埃博拉病毒病临床特征与治疗

埃博拉病毒病(Ebola virus disease,EVD)是由埃博拉病毒引起的烈性传染病,致死率高。EVD临床表现无特异性,确诊主要依靠病原学检查。目前以对症支持治疗为主,其他可能的治疗方案在不断研究探索中。本文对EVD的临床特征及治疗进行综述。     

埃博拉疫苗临床试验研究进展

埃博拉病毒病以往被人们称作埃博拉病毒性出血热,目前尚无针对该病的特异性治疗措施与药物,疫苗成为最有可能预防控制病毒传播的手段。目前,多种埃博拉候选疫苗已经进入了临床试验,包括减毒水疱性口炎病毒载体埃博拉疫苗(rVSV-ZEBOV)、复制缺陷型黑猩猩3型腺病毒载体埃博拉疫苗(cAd3-EBO或ChAd3-EBO-Z)、复制缺陷型人5型腺病毒载体埃博拉疫苗(Ad5-EBOV)和人3型副流感病毒载体埃博拉疫苗(HPIV3)等。ChAd3-EBO-Z和Ad5-EBOV等在早期的临床试验中均表现出较好的安全性和免疫原性。rVSV-ZEBOV率先完成了Ⅲ期临床试验,已证实其对埃博拉病毒病的预防具有很高的保护效力,但是研究数据也提示了该疫苗可能存在的安全性问题。本文旨在回顾2014年以来埃博拉疫苗在临床试验研究方面的重大进展,讨论尚存的问题和挑战以及未来的发展方向。     

抗埃博拉和马尔堡病毒疫苗有望诞生

据金药网6月15日报道，法国等国科学家已经在猴子身上试验成功一种可抵御埃博拉和马尔堡病毒的疫苗，抗埃博拉和马尔堡病毒的人类疫苗有望在不远的未来诞生。埃博拉病毒是引起人类和灵长类动物发生埃博拉出血热的烈性病毒，该病曾在刚果肆虐，并在非洲和欧美国家引起恐慌。     

埃博拉病毒免疫学致病机制研究进展

2014年西非埃博拉病毒病业已成为本年度最严重的公共卫生事件,其暴发迅猛、病死率高、缺乏特效治疗方法和有效疫苗的现状引起了全球的恐慌和卫生医疗领域的高度关注。埃博拉病毒致病主要机制为:感染单核吞噬细胞系统和树突状细胞,导致其大量分泌细胞因子和趋化因子,减少干扰素生成,阻断干扰素作用通路,并诱导多种免疫细胞大量凋亡;诱导多种细胞表面分子表达影响凝血功能;其直接散播和复制同时也能导致大量组织损伤。本文就埃博拉病毒免疫学致病机制研究进展进行综述。     

抗埃博拉病毒药物开发研究进展

埃博拉病毒(Ebola virus)感染引起烈性传染病，即埃博拉出血热，病死率在25%～90%。埃博拉疫情暴发主要集中在非洲地区，目前没有有效的治疗和预防措施，因此急需有效的抗埃博拉药物应用到临床治疗。目前，多家研究机构利用多种药物开发策略筛选抗埃博拉病毒感染的候选药物。已有一部分抗埃博拉药物进入了临床实验研究阶段，但大部分的药物研究仍处在普通细胞实验或动物实验水平。本文从埃博拉分子结构、病毒进入细胞感染方式、抗埃博拉药物研究模型和抗埃博拉药物等方面进行综述，以期望为相关研究提供参考。     

塞拉利昂弗里敦地区老年埃博拉病毒病患者临床特点研究

目的研究塞拉利昂弗里敦地区老年埃博拉病毒病(Ebola virus disease,EVD)患者的临床特点。方法选取我国解放军援塞医疗队2014年10月—2015年3月收治的老年(60岁)EVD确诊患者21例(老年组)进行回顾性分析,研究其临床特点。选取同期收治的非老年EVD患者235例(非老年组)作为对照。结果老年组病毒载量与非老年组差异无统计学意义。老年组主要临床表现依次为发热、乏力、纳差、腹痛、头痛、咳嗽、关节痛、恶心呕吐、腹泻、肌肉痛、胸痛和结膜炎。老年组腹痛(85.7%)和精神错乱(23.8%)的发生率均高于非老年组[64.3%(P=0.047)和8.9%(P=0.047)],关节痛(61.9%)的发生率低于非老年组(83.0%)(P=0.018)。老年组病死率(33.3%)与非老年组(39.1%)差异无统计学意义,老年组入院后至死亡的平均死亡时间[(3.0±1.4)d]与非老年组[(2.3±1.7)d]差异亦无统计学意义。结论老年EVD患者临床表现及预后与非老年EVD患者类似,但仍具有其自身特点,这对诊断和治疗具有重要的指导意义。     

埃博拉病毒病的研究现状

埃博拉病毒病（Ebola virus disease,EVD）是埃博拉病毒（Ebola virus,EBOV）感染引起的一种急性传染病,病死率高达90％［1］。2013年12月暴发于几内亚的高传染性、高致病性、高病死率的 EVD 疫情,是该病被发现38年来规模最大、感染人数和死亡人数最多的一次［2］。2014年8月8日WHO 宣布 EVD 疫情为“国际关注的突发公共卫生事件”。根据 WHO 最新公布的数据,全球因 EVD 死亡患者已经超过1840例,累积确诊、疑似和可能感染病例超过3685例,其中西非三国几内亚、利比里亚和塞拉利昂受影响最为严重,更令人恐惧的是 EVD 已经从非洲扩散至欧洲（西班牙）和美洲（美国）。WHO 预测如果疫情无法得到有效的控制, EVD 的发病数和病死数将在数月内从每周几百例增加至每周几千例,至2014年11月初,西非地区 EVD 患者将超过2万［3］。由于暂无有效的抗病毒药物和疫苗,WHO 已将EBOV 列为生物安全第4级病毒。我国与西非国家在劳务、商务、留学教育等方面人员往来密切,虽然目前国内尚未发生 EVD 疫情,但随时有输入风险,因此有必要加深对该病的科学认识和应对准备。现对 EVD 病原学特征、致病机制、临床表现、诊断、治疗和疫苗研究进展进行综述。     

埃博拉病毒病概述

埃博拉病毒病是由埃博拉病毒感染引起人和灵长类动物的一种以发热、出血和腹泻为主要临床特征的烈性传染病,病死率高达90%。本病于1976年首次发现于非洲的扎伊尔和苏丹,至今已在非洲造成多次大规模的暴发流行。近年来本病已传播至非洲大陆以外的地区,如美国、西班牙、英国和意大利均有发生,这引起了全世界的广泛关注。为了有效防控埃博拉病毒病,本文从病原学、流行病学、临床症状、病理变化以及预防与控制等方面进行概述。     

西非埃博拉病毒病治疗现状

埃博拉病毒病传染性强,病死率高,目前尚无疫苗和特异性药物。现将解放军援塞医疗队塞拉利昂埃博拉留观治疗中心的治疗经验进行总结,并结合文献报道,对一些试验性药物的使用情况及临床试验开展情况进行综述,以期为今后应对该疾病提供依据。     

埃博拉出血热的研究进展

埃博拉出血热(Ebolahemorrhagicfever,EBHF)是埃博拉病毒(Ebolavirus,EBV)引起的人的严重出血性热病。EBV有极高的传染性,有传染性的试验操作要在P4级高度安全实验室中进行。EBHF对人类的危害极大。世界卫生组织将其列为潜在的生物战剂之一,该病毒始发现于扎伊尔北部的埃博拉河     

Ebola virus disease: Recent advances in diagnostics and therapeutics

Ebola virus disease(EVD)is associated with haemorrhagic fever in humans and nonhuman primates,with a high rate of fatality(up to 90%).Some outbreaks in human history have proven the lethality of EVD.The recent epidemic of 2014 and 2015 in West Africa was the deadliest of all time(11 284 deaths).To understand the transmission dynamics,we have reviewed the epidemiology of EVD to date.The absence of any licensed vaccines or approved drugs against Ebola virus(EBOV)further highlights the severity and crisis level of EVD.Some organizations(public and private)are making considerable efforts to develop novel therapeutic approaches or vaccines to contain the outbreak of EBOV shortly.Here,we summarized the various potential drugs and vaccines(undergoing multiple phases of clinical trials)that have arisen as an alternative against EBOV,and we highlighted the numerous issues and limitations hindering this process.Alternatively,an increasing focus on strengthening the medical and civic health structure could provide speedy benefits in containing the spread of EVD,as well as offer a resilient foundation for the deployment of novel drugs and vaccines to the affected countries,once such drugs and vaccines become available.     

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures.     

Being Ready to Treat Ebola Virus Disease Patients

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD.An unprecedented number of health care professionals from a variety of clinical settings, in a wide range of countries are thinking about, preparing for and caring for Ebola virus disease (EVD) patients. Guidance documents on infection prevention and control (IPC) practice and clinical care have been produced by organizations with EVD experience.^1–3 The World Health Organization (WHO) produces guidance for implementation across a wide range of resource settings. Medecin Sans Frontières produces guidance for medical team activities across the outbreak. The Centers for Disease Control and Prevention (CDC) focus on measures which can be taken by the United States health system and extrapolated by others involved in preparedness and response. There are no short cuts to clinical preparedness for EVD. These documents and their revisions should be reviewed carefully.As important as guidance documents are, many lessons must be learned from specific hands-on experience. The WHO has mobilized clinical consultants in support of EVD response in each of the affected countries in West Africa. This short list of key points attempts to consolidate practical lessons learned that do not always percolate into technical documents. Having landed in unconstrained, resource-limited settings at the start of local EVD clinical operations in an outbreak, and more established EVD care centers, we hope that others might adopt some of these lessons and avoid some of the risks inherent to the steep learning curve associated with delivering EVD care. The points are geared toward the daily care of patients as opposed to the critical mechanics of establishing a care center and developing its procedures. They are focused on the outbreak setting and also have relevance to the referral hospital setting.     

An Improved Ward Architecture for Treatment of Patients with Ebola Virus Disease in Liberia

During the recent outbreak of Ebola virus disease (EVD) in west Africa, we established an Ebola treatment center (ETC) with improved ward architecture. The ETC was built with movable prefabricated boards according to infectious disease unit standard requirements. The clinical staff ensured their own security while providing patients with effective treatment. Of the 180 admissions to the ETC, 10 cases were confirmed with EVD of which six patients survived. None of the clinical staff was infected. We hope that our experience will enable others to avoid unnecessary risks while delivering EVD care.     

埃博拉出血热研究现状及2014年疫情进展

发现于1976年的埃博拉出血热具有高传染性、高致病性和高病死率的特点,曾多次在非洲中西部暴发流行,病死率高达50％-90％。然而目前仍然未研制出有效的疫苗和抗病毒药物。始于2014年初的非洲西部暴发疫情是该病历史上最严重的疫情,感染和死亡人数已经超过了该病发现以来的总和,WHO宣布本次疫情为“国际关注的突发公共卫生事件”。国际公共卫生和医疗部门正在通力合作抗击这一烈性传染病。本文就该病研究现状及本次疫情暴发以来的一些特点进行回顾。     

Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control

Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013–2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks.We live in a globally interconnected world where the rapidity of modern travel allows us, and the microbes that infect us, to be virtually anywhere within only hours. In earlier times, weeks or months were often needed to traverse the barriers that were imposed by geography and distance. The lengthiness of travel afforded some protection against the introduction of virulent pathogens to new locales because many who were infected either recovered or succumbed before reaching their final destination. This is no longer the case. Several tropical viral diseases (e.g., dengue, Middle East respiratory syndrome, chikungunya, and Ebola virus disease [EVD]) have expanded their geographical range due in part to transit of infected humans.¹ Of these diseases, EVD has received the lion''s share of international attention. This is because of the 2013–2015 EVD outbreak in west Africa where over 27,000 cases with more than 11,000 deaths have been reported.² Although EVD transmission rates have decreased and Liberia was recently declared free of EVD transmission by the World Health Organization (WHO), this crisis continues to threaten global health and security.EVD is caused by infection with a single-stranded, negative-sense RNA virus of the genus Ebolavirus.³ Zaire ebolavirus (EBOV) was first identified in humans in an outbreak that occurred in 1976 near the Ebola River in the Democratic Republic of the Congo (DRC, formerly Zaire).⁴ Three additional African species, Sudan, Tai Forest, and Bundibugyo ebolavirus, also cause disease in humans, but the case fatality rates due to infection with these viruses are not as high as that due to EBOV, which can reach 90%. Although the natural reservoir of Ebola virus has not been definitively determined, serological and molecular data indicate that this virus is present in some species of African frugivorous and insectivorous bats.^5–7 Zoonotic transmission of Ebola virus may occur in humans who are exposed during hunting and butchering of infected bats.^5,8 Increases in human population, coupled with changes in land use, enhance the risk of contact with reservoirs of Ebola virus.⁸ Pigott and others⁶ mapped the zoonotic niche of EVD in central and west Africa and reported that 22 million humans inhabit at-risk areas. It is possible that EVD could spread more readily in these areas because of increasing population growth and mobility.Human-to-human transmission of EVD occurs primarily via direct contact with bodily fluids of an infected human after fever has developed or with the body of a human who has recently died of EVD.³ The incubation period usually lasts about 1 week, but can be 3 weeks or possibly longer. Thus, humans who are incubating disease, but not yet symptomatic, can travel a considerable distance before they begin to shed the virus as demonstrated by the introduction of EVD via ground travel (e.g., Guinea to Liberia, Sierra Leone, and Senegal) and via air travel (e.g., Guinea to the United States; Liberia to Nigeria, the United States, and the United Kingdom; Sierra Leone to Italy).^2,9,10Although the current EVD outbreak has waned, infections are still occurring in some hot spots in west Africa. Because of the international connectivity of west Africa, there is concern that EVD could spread to other densely populated, resource-limited areas of the world that are ill-prepared to control this disease for which there is as yet no licensed vaccine or proven curative therapy.^10–13 Halting EVD transmission is critical to prevent further spread of EVD within and beyond west Africa. The use of multifaceted non-pharmaceutical interventions (e.g., infection control practices, EVD treatment units for case isolation, contact tracing with follow-up and quarantine, sanitary burial, health education) has decreased EVD transmission in many areas of west Africa. Nevertheless, delays in diagnosing and reporting new EVD cases in less accessible rural areas continue to hamper control efforts.¹⁴If control interventions had been deployed early on, the EVD outbreak in west Africa may have been contained in a relatively short time similar to some EVD outbreaks that occurred previously in central Africa.^15,16 Unfortunately, the lack of surveillance for EVD in west Africa, a region that was largely unfamiliar with this disease, and the lack of adequate public health capacity, impeded an early response and allowed the establishment of multiple foci of EVD in Guinea. However, there is hope that new advances in rapid diagnostics and mobile-based communication technology will expedite the deployment of resources to control EVD outbreaks.^1,17,18 Rapid diagnosis of EVD is critical because the early symptoms of EVD (i.e., high fever, malaise, fatigue, body aches) can be confused with those of some other endemic infectious diseases (e.g., malaria, influenza, typhoid, dengue, yellow fever, Lassa fever).^19,20 The WHO recently approved the ReEBOV Antigen Rapid Test, developed by Tulane University researchers (New Orleans, LA) in partnership with Corgenix Inc. (Broomfield, CO), for procurement in EVD-affected countries.²¹ This lateral flow immunochromatographic assay can provide results within 15–25 minutes and is based on the qualitative detection of EBOV VP40 antigen in serum, plasma, or finger-stick whole blood.²² Although less accurate (92% sensitivity; 85% specificity) than “gold standard” nucleic acid amplification tests (NAATs), the ReEBOV Antigen Rapid Test is less expensive, easier to perform, and does not require electricity. With appropriate infection control precautions, the ReEBOV Antigen Rapid Test can be used by trained personnel as a screening tool in rural health clinic settings for presumptive detection of EBOV in patients whose signs and symptoms, in conjunction with epidemiological risk factors, are consistent with EVD. Rapid diagnosis of presumptive EVD cases allows for 1) isolation of symptomatic individuals while they await confirmatory NAAT to prevent health-care-associated EVD; 2) quarantine and monitoring of contacts to prevent spread of EVD to the community; 3) early administration of supportive treatments (i.e., rehydration, electrolytes, antibiotics, antimalarials) to improve patient outcome; and 4) timely engagement of affected communities to reduce fear and to encourage cooperation with control interventions. However, because of the lower specificity of the ReEBOV Antigen Rapid Test, further refinements will be necessary to improve its positive predictive value when EVD case numbers are low to reduce exposure of patients with false positive test results to patients with EVD. The U.K.''s Defense Science and Technology Laboratory (DSTL) has developed a rapid diagnostic test (RDT) that is similar in principle to the ReEBOV Antigen Rapid Test, but is based on detection of an undisclosed Ebola virus antigen.²³ The DSTL EVD RDT can produce a semiquantitative result by scoring the test (T) line on color intensity (2–10). Although the DSTL EVD RDT appears to have high sensitivity (100%) with a specificity of (∼92–97%) compared with NAAT (i.e., when the control and T line (CT) score is above 2, 4, or 6), further studies are needed before this test can be approved for screening purposes. Other RDTs for EVD are in various stages of development. For example, researchers at the Massachusetts Institute of Technology (Cambridge, MA) and Harvard Medical School (Boston, MA) engineered a multiplexed pathogen detection platform that uses multicolored silver nanoparticles conjugated to monoclonal antibodies directed against EBOV, dengue virus, or yellow fever virus to detect the presence of these agents in human serum.²⁴ Further development of this experimental device, with inclusion of monoclonal antibodies directed against malaria, a common endemic infection, may result in a rapid screening test that could aid differential diagnosis of febrile patients who are suspected to have EVD.Once presumptive EVD cases have been identified, they must be promptly reported to public health authorities to quickly mobilize resources for outbreak control. Advances in mobile-based communication technology are enabling faster, cheaper, and more reliable reporting of EVD cases with expanded geographic coverage. One of several promising examples is mHero (mobile Health Worker Electronic Response and Outreach), a new, two-way, mobile communication platform.²⁵ IntraHealth International (Chapel Hill, NC), in partnership with the United Nations Children''s Fund and Liberia''s Ministry of Health and Social Welfare (MOHSW), has deployed mHero to help frontline health workers (HWs) respond to EVD outbreaks. mHero enables Liberia''s MOHSW to instantly send critical information to thousands of HWs'' mobile phones and HWs to send time-sensitive information to the MOHSW. This powerful tool allows for reporting and tracking of new EVD cases, communicating laboratory test results, sharing reference and training materials, testing and improving HWs'' knowledge, and coordinating with rural health clinics. IntraHealth is introducing mHero in Guinea and discussions are underway to roll out mHero to other countries in west Africa.In addition to expediting EVD case reporting, advances in mobile-based communication technology could help to track the spread of EVD. Accurate, near real-time information on population mobility in west Africa, one of the most highly connected and densely populated regions of Africa, could show where people have gone after leaving an area of EVD transmission, thus suggesting where new cases might appear. This information is valuable because it enables public health authorities to rapidly focus intervention efforts to interrupt EVD transmission. Only a decade ago, obtaining detailed and comprehensive data for this region would have been impossible. Today, call data records (CDRs) that contain mobility data are stored on cell phone carrier servers. Although CDRs have yet to be released for Guinea, Liberia, and Sierra Leone, the west African countries most affected by the EVD outbreak, mobility pattern models have been generated for Côte d''Ivoire and Senegal to demonstrate the feasibility of this approach, which has been previously used to track the spread of malaria in Kenya and cholera in Haiti.²⁶Thus far, more than 24 outbreaks of EVD have occurred in Africa since the first documented outbreak in the DRC in 1976. The 2013–2015 EVD outbreak in west Africa is a stark reminder that an emerging infectious disease can exact a terrible toll on human life, severely affect health-care systems, devastate fragile economies, and destabilize governments. Because Ebola virus has an animal reservoir, it cannot be eradicated. Zoonotic introduction of Ebola virus into the African population will continue to occur and must be detected and tackled early on at the source to prevent amplification of sporadic EVD cases into large-scale outbreaks that are driven by human to human transmission.^7,27 Improved rapid diagnostics and mobile-based communication technology are critical to enable a swift response to EVD and must be included in the EVD preparedness response. Finally, the current EVD outbreak has highlighted the urgent need to rebuild the greatly weakened public health infrastructure of EVD-affected west Africa. This will require a long-term international commitment of significant financial and technical resources. Nonetheless, investments along these lines will surely pay off many times over for global health by strengthening west Africa''s capacity to mount an early response to control outbreaks of EVD and other emerging infectious diseases.     

From the Cover: Human Ebola virus infection results in substantial immune activation

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.Ebola virus is a member of the Filoviridae family, which are filamentous, negative-stranded RNA viruses that are known to cause severe human disease (1). An ongoing outbreak of Ebola virus in West Africa has brought this virus and the disease it causes (Ebola virus disease; EVD) to the forefront. The World Health Organization has reported over 20,000 cases and 8,000 deaths in West Africa, with Sierra Leone, Guinea, and Liberia the most affected.Our knowledge of the human immune response to Ebola virus has been severely limited due to the lack of infrastructure to perform such analyses in high containment levels (biosafety level 4; BSL-4). Minimal data exist regarding the human cellular immune response during acute Ebola virus infection, which indicate that aberrant cytokine responses (2–6), decreased CD4 and CD8 T cells, and increased CD95 expression on T cells are all associated with fatal outcomes (4). In vivo studies have revealed an association between apoptosis of lymphocytes and fatal outcome (3), and lymphocyte apoptosis has been seen both in vitro in infected human cells and in vivo in mouse and nonhuman primate models (7–9).The natural serologic response to Ebola virus infection has been well-characterized, with specific IgM responses detected as early as 2 d after symptom onset but generally occurring 10–29 d after symptom onset in most patients. Ebola virus-specific IgG responses have been detected as early as 6 d post symptom onset, occurring ∼19 d after symptom onset in most individuals (10, 11). Serological responses to Ebola virus have been reported as absent or diminished in fatal cases; however, sample sizes have been very limited (3).Data from in vitro studies have demonstrated that Ebola virus-infected dendritic cells are impaired in their ability to produce cytokines and activate autologous T cells (12), whereas infected macrophages exhibit impaired maturation (13). Ebola virus also encodes several proteins that can interfere with the innate immune response in infected cells (14). These in vitro studies, combined with the limited human data showing T-cell apoptosis, lymphopenia, and absent antibody responses in fatal cases, have led to the assumption that Ebola virus infection is immunosuppressive.Here we examine the immune responses of four survivors of EVD who received care at Emory University Hospital. This first look, to our knowledge, at the human adaptive immune response during the acute phase of Ebola virus infection shows striking levels of T- and B-cell activation in all four patients.