RESUMO
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.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Imunidade Celular/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Ebolavirus/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/virologia , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunofenotipagem , Interferon gama/imunologia , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Células Precursoras de Linfócitos B/imunologia , Células Precursoras de Linfócitos B/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Virais/imunologia , Proteínas Virais/metabolismoRESUMO
Vaccination against Ebola virus disease is a tool that may limit disease transmission and deaths in future outbreaks, integrated within traditional Ebola outbreak prevention and control measures. Although a licensed Ebolavirus vaccine (EV) is not yet available, the 2014-2016 West African Ebola outbreak has accelerated EV clinical trials and given public health authorities in Guinea, Liberia, and Sierra Leone experience with implementation of emergency ring vaccination. As evidence supporting the use of EV during an outbreak response has become available, public health authorities in at-risk countries are considering how to integrate EV into future emergency Ebola responses and for prevention in high-risk groups, such as healthcare workers and frontline workers (HCW/FLWs), even before an EV is licensed. This review provides an overview of Ebola epidemiology, immunology, and evidence to inform regional and country-level decisions regarding EV delivery during an emergency response and to at-risk populations before a licensed vaccine is available and beyond. Countries or regions planning to use EV will need to assess factors such as the likelihood of a future Ebolavirus outbreak, the most likely species to cause an outbreak, the availability of a safe and effective EV (unlicensed or licensed) for the affected population, capacity to implement Ebola vaccination in conjunction with standard Ebola outbreak control measures, and availability of minimum essential resources and regulatory requirements to implement emergency Ebola vaccination. Potential emergency vaccination strategies for consideration include ring or geographically targeted community vaccination, HCW/FLW vaccination, and mass vaccination. The development of guidelines and protocols for Ebola vaccination will help ensure that activities are standardized, evidence-based, and well-coordinated with overall Ebola outbreak response efforts in the future.
Assuntos
Surtos de Doenças/prevenção & controle , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Emergências , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Planejamento em Saúde Comunitária , Tomada de Decisões , Vacinas contra Ebola/administração & dosagem , Serviços Médicos de Emergência , Geografia Médica , Humanos , VacinaçãoRESUMO
As the Ebola outbreak in West Africa wanes, it is time for the international scientific community to reflect on how to improve the detection of and coordinated response to future epidemics. Our interdisciplinary team identified key lessons learned from the Ebola outbreak that can be clustered into three areas: environmental conditions related to early warning systems, host characteristics related to public health, and agent issues that can be addressed through the laboratory sciences. In particular, we need to increase zoonotic surveillance activities, implement more effective ecological health interventions, expand prediction modeling, support medical and public health systems in order to improve local and international responses to epidemics, improve risk communication, better understand the role of social media in outbreak awareness and response, produce better diagnostic tools, create better therapeutic medications, and design better vaccines. This list highlights research priorities and policy actions the global community can take now to be better prepared for future emerging infectious disease outbreaks that threaten global public health and security.
Assuntos
Controle de Doenças Transmissíveis/organização & administração , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Surtos de Doenças/prevenção & controle , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Saúde Pública , Saúde Global , HumanosRESUMO
A number of "new" (emerging) infections that can also cause inflammatory eye changes are appearing and becoming increasingly important. In the past, diseases such as chikungunya, dengue fever or West Nile virus infections were endemic in tropical regions, but are now expanding worldwide and causing significant morbidity and even mortality. "Globalization" and human migration are important factors leading to the import of these infections. Climate changes are probably even more important. Increasing temperatures provide suitable conditions for new vectors, and may lead to autochthonous transmission of infectious pathogens. Diagnosis of these diseases requires not only careful assessment of medical and travel history, but also the application of specific laboratory diagnostic tests. A broad spectrum of ocular involvement has been reported, with frequent posterior segment involvement. Emerging infections should therefore be considered in the differential diagnosis of retinitis, chorioretinitis, retinal vasculitis and optic neuropathy in a patient living in or traveling back from an endemic area. Since these infections are often vector (insect) borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and initiation of supportive care. Here, we focus on Chikungunya, Dengue fever, Ebola fever, the West Nile virus and Rickettsioses, which frequently demonstrate ocular involvement.