Safety of Recombinant VSV–Ebola Virus Vaccine Vector in Pigs

The ongoing Ebola outbreak in West Africa has resulted in fast-track development of vaccine candidates. We tested a vesicular stomatitis virus vector expressing Ebola virus glycoprotein for safety in pigs. Inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs.     

Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo

We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus.     

两种出血热病毒新型液相芯片检测体系的建立

目的 建立两种出血热生物恐怖病毒(马尔堡病毒、埃博拉病毒)的新型液相芯片检测方法.方法针对马尔堡病毒、扎伊尔埃博拉病毒的特异性基因序列设计2对引物和相应的TSPE引物.经多重PCR扩增之后、加入连有TAG的TSPE引物特异性识别靶目标,标记有生物素的dCTP加入到延伸序列中,TAG与微球上的anti-TAG互补,SAP...     

Feasibility of Xpert Ebola Assay in Médecins Sans Frontières Ebola Program,Guinea

Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.     

Potential mammalian filovirus reservoirs

Ebola and Marburg viruses are maintained in unknown reservoir species; spillover into human populations results in occasional human cases or epidemics. We attempted to narrow the list of possibilities regarding the identity of those reservoir species. We made a series of explicit assumptions about the reservoir: it is a mammal; it supports persistent, largely asymptomatic filovirus infections; its range subsumes that of its associated filovirus; it has coevolved with the virus; it is of small body size; and it is not a species that is commensal with humans. Under these assumptions, we developed priority lists of mammal clades that coincide distributionally with filovirus outbreak distributions and compared these lists with those mammal taxa that have been tested for filovirus infection in previous epidemiologic studies. Studying the remainder of these taxa may be a fruitful avenue for pursuing the identity of natural reservoirs of filoviruses.     

Status and challenges of filovirus vaccines

Vaccines that could protect humans against the highly lethal Marburg and Ebola viruses have eluded scientists for decades. Classical approaches have been generally unsuccessful for Marburg and Ebola viruses and pose enormous safety concerns as well. Modern approaches, in particular those using vector-based approaches have met with success in nonhuman primate models although success against Ebola has been more difficult to achieve than Marburg. Despite these successes, more work remains to be done. For the vector-based vaccines, safety in humans and potency in the face of pre-existing anti-vector immunity may be critical thresholds for licensure. The immunological mechanism(s) by which these vaccines protect has not yet been convincingly determined. Licensure of these vaccines for natural outbreaks may be possible through clinical trials although this will be very difficult; licensure may also be possible by pivotal efficacy studies in animal models with an appropriate challenge. Nevertheless, nonhuman primate studies have shown that protection against Marburg and Ebola is possible and there is hope that one day a vaccine will be licensed for human use.     

Regional Spread of Ebola Virus,West Africa, 2014

To explain the spread of the 2014 Ebola epidemic in West Africa, and thus help with response planning, we analyzed publicly available data. We found that the risk for infection in an area can be predicted by case counts, population data, and distances between affected and nonaffected areas.     

Haemorrhagic fever in Gabon. I. Incidence of Lassa,Ebola and Marburg viruses in Haut-Ogooué

A serological enquiry aimed at determining the incidence of infection with Lassa, Ebola and Marburg viruses was conducted on the human population of the region of Haut-Ogooué (Gabon) and on primates.The results, obtained by the indirect immunofluorescence technique, showed that more than 6% of the human population had had contact with Ebola virus but no antibodies against Marburg or Lassa viruses were found.Most sera reacted to an Ebola antigen from a Zairian strain, but showed little or no reaction to an antigen from a Sudanese strain.     

Shedding of Marburg Virus in Naturally Infected Egyptian Rousette Bats,South Africa, 2017

We detected Marburg virus RNA in rectal swab samples from Egyptian rousette bats in South Africa in 2017. This finding signifies that fecal contamination of natural bat habitats is a potential source of infection for humans. Identified genetic sequences are closely related to Ravn virus, implying wider distribution of Marburg virus in Africa.     

Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection

Ongoing outbreaks of filoviruses in Africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. We previously reported the generation of virus-like particles (VLPs) for the filoviruses, Marburg (MARV) and Ebola (EBOV) virus, and that vaccinating mice with Ebola VLPs (eVLPs) results in complete survival from a lethal EBOV challenge. The objective of this study was to determine the efficacy of Marburg VLPs (mVLPs) as a potential vaccine against lethal MARV infection in a guinea pig model. Guinea pigs vaccinated with mVLPs or inactivated MARV developed MARV-specific antibody titers, as tested by ELISA or plaque-reduction and neutralization assays and were completely protected from a MARV challenge over 2000 LD50. While eVLP vaccination induced high EBOV-specific antibody responses, it did not cross-protect against MARV challenge in guinea pigs. Vaccination with mVLP or eVLP induced proliferative responses in vitro only upon re-exposure to the homologous antigen and this recall proliferative response was dependent on the presence of CD4+ T cells. Taken together with our previous work, these findings suggest that VLPs are a promising vaccine candidate for the deadly filovirus infections.     

Postmortem Stability of Ebola Virus

The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus–infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks.     

Marburg, Ebola and Rift Valley Fever virus antibodies in East African primates

Sera from 464 primates held at four institutes in Kenya were tested by indirect immunofluorescence for the presence of antibodies against Marburg, Ebola, Congo haemorrhagic fever, Rift Valley fever and Lassa viruses. Four of 136 vervet monkeys were positive for Marburg virus antibodies and three of 184 baboons had antibodies against Ebola virus. One baboon was positive for Marburg virus antibodies. Two vervet monkeys, three baboons and one grivet monkey (of 56 tested) had antibodies against Rift Valley fever virus. No Congo or Lassa virus antibodies were detected. A sample of 88 sera of more arboreal primates (Sykes, blue and colobus monkeys) were negative against all five antigens, as were sera from 58 staff members of the institutes who worked with or near the animals.     

The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak

Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.     

Risk Prediction Score for Pediatric Patients with Suspected Ebola Virus Disease

Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014–2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018–2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use.     

Antibodies against haemorrhagic fever viruses in Kenya populations

Human sera from Lodwar (77 sera), Nzoia (841 sera), Masinga (251 sera), Laisamis (174 sera) and the Malindi/Kilifi area (556 sera) in Kenya were tested by indirect immunofluorescence for antibodies against Marburg, Ebola (Zaire and Sudan strains), Congo haemorrhagic fever, Rift Valley fever and Lassa viruses. Antibodies against Ebola virus, particularly the Zaire strain, were detected in all regions and were, over-all, more abundant than antibodies against the other antigens. Ebola and Marburg antibody prevalence rates were highest in the samples from Lodwar and Laisamis, both semi-desert areas. Antibodies against Rift Valley fever virus were also highest in the Lodwar sample followed by Malindi/Kilifi and Laisamis. Congo haemorrhagic fever virus antibodies were rare and no antibodies against Lassa virus were detected in the 1899 sera tested.     

Infections by viruses of the families Bunyaviridae and Filoviridae

Rift Valley fever is the most important bunyaviral disease of animals in Africa. The virus, transmitted by mosquitoes, causes abortions and mortality in young animals in addition to haemorrhagic fevers in humans. Although vaccines against this virus are available, the uses of these vaccines are limited because of deleterious effects or incomplete protection, justifying further studies to improve the existing vaccines or to develop others. Nairobi sheep disease is transmitted by ticks. The disease is endemic in East Africa and sporadic cases are reported in India and Sri Lanka. Other viruses transmitted by mosquitoes or midges are teratogenic in cattle or sheep, these include Akabane and related viruses in Asia, Australia and the Middle East, and Cache Valley in North America. The Marburg and Ebola viruses of the genus Filovirus are associated with epidemics in Central Africa with high fatality rates in humans; some outbreaks were related to contact with monkeys. Another subtype of Ebola virus was first described in a quarantine facility in the United States of America among cynomolgus monkeys (Macaca fascicularis) from the Philippines. The reservoir of these viruses remains unknown.     

Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands

On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact.     

埃博拉病毒病的发病机制和诊疗策略

埃博拉病毒是一种强致死性病原体,可引起类似于感染性休克的严重出血热——埃博拉病毒病。埃博拉病毒病在2014年西非地区发生历史上最大的大流行疫情,其临床特点为凝血功能障碍、毛细血管渗漏综合征和休克。迄今为止尚无针对性抗病毒药物治疗。本文从病原学、感染途径、发病机制、临床特征、辅助检查、诊断及治疗特点等方面探讨埃博拉病毒病的机制和诊疗策略。     

Research Ethics and International Epidemic Response: The Case of Ebola and Marburg Hemorrhagic Fevers

Outbreaks of filovirus (Ebola and Marburg) hemorrhagic feversin Africa are typically the theater of rescue activities involvinginternational experts and agencies tasked with reinforcing nationalauthorities in clinical management, biological diagnosis, sanitation,public health surveillance and coordination. These outbreakscan be seen as a paradigm for ethical issues posed by epidemicemergencies, through the convergence of such themes as: isolationand quarantine, privacy and confidentiality and the interpretationof ethical norms across different ethnocultural settings. Withan emphasis on the boundaries between public health investigationsand research, this article reviews specific challenges, pastpractices and current normative documents relevant to the applicationof ethical standards in the course of outbreaks of filovirushemorrhagic fevers. Aside from commonly identified issues ofinformed consent and institutional review processes, we arguefor more clarity over the specification of which communitiesare expected to share benefits, and we advocate for the useof collective definitions of duty to care and standard of care.We propose new elaborations around existing normative instruments,and we suggest some pathways toward more comprehensive approachesto the ethics of research in outbreak situations.     

Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and Delayed Transmission Control

While the ongoing Ebola outbreak continues in the West Africa countries of Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new introductions of Ebola from infected evacuees or travelers. We analyzed transmission data from patients (i.e., evacuees, international travelers, and those with locally acquired illness) in countries other than the 3 with continuing Ebola epidemics and quantitatively assessed the outbreak risk from new introductions by using different assumptions for transmission control (i.e., immediate and delayed). Results showed that, even in countries that can quickly limit expected number of transmissions per case to <1, the probability that a single introduction will lead to a substantial number of transmissions is not negligible, particularly if transmission variability is high. Identifying incoming infected travelers before symptom onset can decrease worst-case outbreak sizes more than reducing transmissions from patients with locally acquired cases, but performing both actions can have a synergistic effect.