RESUMO
OBJECTIVE: Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion. SETTING: From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP. PARTICIPANTS: All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible. RESULTS: No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens. CONCLUSIONS: Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
Assuntos
Anticorpos Antivirais/sangue , Infecção Hospitalar/sangue , Infecção Hospitalar/epidemiologia , Doença pelo Vírus Ebola/sangue , Febre Lassa/sangue , Centros Médicos Acadêmicos , Adulto , Infecção Hospitalar/prevenção & controle , Feminino , Georgia/epidemiologia , Pessoal de Saúde , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Controle de Infecções/métodos , Febre Lassa/prevenção & controle , Vírus Lassa , Masculino , Pessoa de Meia-Idade , Estados Unidos , Vacinas Virais/imunologiaRESUMO
A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.
Assuntos
Catarata , Ebolavirus , Doença pelo Vírus Ebola , Olho , Humanos , Pessoa de Meia-Idade , SobreviventesRESUMO
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/metabolismoRESUMO
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.
Assuntos
Doença pelo Vírus Ebola/diagnóstico , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Aleitamento Materno , Parto Obstétrico , Surtos de Doenças , Feminino , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/transmissão , Humanos , Controle de Infecções , Gravidez , Complicações Infecciosas na Gravidez/terapia , SobreviventesRESUMO
Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.
Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Febre Lassa , Pirazinas/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Humanos , Febre Lassa/tratamento farmacológico , Febre Lassa/fisiopatologia , Febre Lassa/virologia , Vírus Lassa/genética , Masculino , Reação em Cadeia da Polimerase , RNA Viral/análise , RNA Viral/genética , TogoRESUMO
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/sangueRESUMO
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.
Assuntos
Centers for Disease Control and Prevention, U.S. , Doença pelo Vírus Ebola/prevenção & controle , Controle de Infecções/métodos , África Ocidental , Atenção à Saúde , Surtos de Doenças , Ebolavirus , Humanos , Nebraska , Estados UnidosRESUMO
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).
Assuntos
Recursos em Saúde/provisão & distribuição , Doença pelo Vírus Ebola/terapia , Pessoal de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Doença pelo Vírus Ebola/economia , Humanos , Equipamento de Proteção Individual/provisão & distribuiçãoAssuntos
Infecções Oculares Virais/tratamento farmacológico , Doença pelo Vírus Ebola/tratamento farmacológico , Doenças da Íris/tratamento farmacológico , Pan-Uveíte/tratamento farmacológico , Transtornos da Pigmentação/tratamento farmacológico , Administração Oral , Adulto , Amidas/uso terapêutico , Atropina/uso terapêutico , Combinação de Medicamentos , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/virologia , Fluprednisolona/análogos & derivados , Fluprednisolona/uso terapêutico , Glucocorticoides/uso terapêutico , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Injeções Intraoculares , Doenças da Íris/diagnóstico , Doenças da Íris/virologia , Masculino , Microscopia Acústica , Imagem Multimodal , Midriáticos/uso terapêutico , Soluções Oftálmicas , Pan-Uveíte/diagnóstico , Pan-Uveíte/virologia , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/virologia , Prednisona/uso terapêutico , Pirazinas/uso terapêutico , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Sobreviventes , Triancinolona Acetonida/uso terapêutico , Corpo Vítreo/virologiaRESUMO
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.
Assuntos
Doenças Transmissíveis/epidemiologia , Surtos de Doenças/prevenção & controle , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola , Controle de Infecções/métodos , África Ocidental/epidemiologia , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/uso terapêutico , Doenças Transmissíveis/transmissão , Vacinas contra Ebola/imunologia , Vacinas contra Ebola/uso terapêutico , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/transmissão , Humanos , Terapias em Estudo/métodos , Estados Unidos/epidemiologia , Uveíte/microbiologiaRESUMO
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 , ViremiaRESUMO
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 , SobreviventesRESUMO
David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States.
Assuntos
Doença pelo Vírus Ebola/terapia , Controle de Infecções/organização & administração , Tomada de Decisões , Surtos de Doenças/história , Georgia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/história , História do Século XXI , Hospitais Universitários , Humanos , Isolamento de Pacientes/organização & administraçãoRESUMO
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/virologiaRESUMO
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 , NebraskaRESUMO
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/terapiaRESUMO
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 , MasculinoRESUMO
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 UnidosRESUMO
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.