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Background: Recent outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD) in sub-Saharan Africa illustrate the need to better understand animal reservoirs, burden of disease, and human transmission of filoviruses. This protocol outlines a systematic literature review to assess the prevalence of filoviruses that infect humans in sub-Saharan Africa. A secondary aim is to qualitatively describe and evaluate the assays used to assess prevalence., Methods: The data sources for this systematic review include PubMed, Embase, and Web of Science. Titles, abstracts, and full texts will be reviewed for inclusion by a primary reviewer and then by a team of secondary reviewers, and data will be extracted using a pre-specified and piloted data extraction form. The review will include human cross-sectional studies, cohort studies, and randomized controlled trials conducted in sub-Saharan Africa up until March 13, 2024 that have been published in peer-reviewed scientific journals, with no language restrictions. Prevalence will be stratified by pathogen, population, assay, and sampling methodology and presented in forest plots with estimated prevalence and 95% confidence intervals. If there are enough studies within a stratum, I 2 statistics will be calculated (using R statistical software), and data will be pooled if heterogeneity is low. In addition, assays used to detect infection will be evaluated. All studies included in the review will be assessed for quality and risk of bias using the JBI Prevalence Critical Appraisal Tool and for certainty using the GRADE certainty ratings., Discussion: Accurately measuring the rate of exposure to filoviruses infecting humans in sub-Saharan Africa using prevalence provides an essential understanding of natural history, transmission, and the role of subclinical infection. This systematic review will identify research gaps and provide directions for future research seeking to improve our understanding of filovirus infections. Understanding the natural history, transmission, and the role of subclinical infection is critical for predicting the impact of an intervention on disease burden., Systematic Review Registration: In accordance with the guidelines outlined in the PRISMA-P methodology, this protocol was registered with PROSPERO on April 7, 2023 (ID: CRD42023415358)., (© 2024. The Author(s).)

Filoviruses are negative-sense single-stranded RNA viruses often associated with severe and highly lethal hemorrhagic fever in humans and nonhuman primates, with case fatality rates as high as 90%. Of the known filoviruses, Ebola virus (EBOV), the prototype of the genus Orthoebolavirus , has been a major public health concern as it frequently causes outbreaks and was associated with an unprecedented outbreak in several Western African countries in 2013-2016, affecting 28,610 people, 11,308 of whom died. Thereafter, filovirus research mostly focused on EBOV, paying less attention to other equally deadly orthoebolaviruses (Sudan, Bundibugyo, and Taï Forest viruses) and orthomarburgviruses (Marburg and Ravn viruses). Some of these filoviruses have emerged in nonendemic areas, as exemplified by four Marburg disease outbreaks recorded in Guinea, Ghana, Tanzania, and Equatorial Guinea between 2021 and 2023. Similarly, the Sudan virus has reemerged in Uganda 10 years after the last recorded outbreak. Moreover, several novel bat-derived filoviruses have been discovered in the last 15 years (Lloviu virus, Bombali virus, Měnglà virus, and Dehong virus), most of which are poorly characterized but may display a wide host range. These novel viruses have the potential to cause outbreaks in humans. Several gaps are yet to be addressed regarding known and emerging filoviruses. These gaps include the virus ecology and pathogenicity, mechanisms of zoonotic transmission, host range and susceptibility, and the development of specific medical countermeasures. In this review, we summarize the current knowledge on non-Ebola filoviruses (Bombali virus, Bundibugyo virus, Reston virus, Sudan virus, Tai Forest virus, Marburg virus, Ravn virus, Lloviu virus, Měnglà virus, and Dehong virus) and suggest some strategies to accelerate specific countermeasure development.

Ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (NHPs). While some bat species are suspected to be natural reservoirs of these filoviruses, wild NHPs often act as intermediate hosts for viral transmission to humans. Using an enzyme-linked immunosorbent assay, we screened two NHP species, wild baboons and vervet monkeys captured in Zambia, for their serum IgG antibodies specific to the envelope glycoproteins of filoviruses. From 243 samples tested, 39 NHPs (16%) were found to be seropositive either for ebolaviruses or marburgviruses with endpoint antibody titers ranging from 100 to 25,600. Interestingly, antibodies reactive to Reston virus, which is found only in Asia, were detected in both NHP species. There was a significant difference in the seropositivity for the marburgvirus antigen between the two NHP species, with baboons having a higher positive rate. These results suggest that wild NHPs in Zambia might be nonlethally exposed to these filoviruses, and this emphasizes the need for continuous monitoring of filovirus infection in wild animals to better understand the ecology of filoviruses and to assess potential risks of outbreaks in humans in previously nonendemic countries.

Bat-borne zoonotic pathogens belonging to the family Paramxyoviridae, including Nipah and Hendra viruses, and the family Filoviridae, including Ebola and Marburg viruses, can cause severe disease and high mortality rates on spillover into human populations. Surveillance efforts for henipaviruses and filoviruses have been largely restricted to the Old World; however, recent studies suggest a potentially broader distribution for henipaviruses and filoviruses than previously recognized. In the current study, we screened for henipaviruses and filoviruses in New World bats collected across 4 locations in Trinidad near the coast of Venezuela. Bat tissue samples were screened using previously established reverse-transcription polymerase chain reaction assays. Serum were screened using a multiplex immunoassay to detect antibodies reactive with the envelope glycoprotein of viruses in the genus Henipavirus and the family Filoviridae. Serum samples were also screened by means of enzyme-linked immunosorbent assay for antibodies reactive with Nipah G and F glycoproteins. Of 84 serum samples, 28 were reactive with ≥1 henipavirus glycoprotein by ≥1 serological method, and 6 serum samples were reactive against ≥1 filovirus glycoproteins. These data provide evidence of potential circulation of viruses related to the henipaviruses and filoviruses in New World bats., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Bats are reservoirs for several zoonotic pathogens, including filoviruses. Recent work highlights the diversity of bat borne filoviruses in Asia. High risk activities at the bat-human interface pose the threat of zoonotic virus transmission. We present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus surface glycoproteins by screening sera in a multiplexed serological assay. Antibodies reactive to two antigenically distinct filoviruses were detected in human sera and to three individual filoviruses in bats in remote Northeast India. Sera obtained from Eonycteris spelaea bats showed similar patterns of cross-reactivity as human samples, suggesting them as the species responsible for the spillover. In contrast, sera from Rousettus leschenaultii bats reacted to two different virus glycoproteins. Our results indicate circulation of several filoviruses in bats and the possibility for filovirus transmission from bats to humans., Competing Interests: The authors have declared that no competing interests exist.

Although Lloviu virus (LLOV) was discovered in the carcasses of insectivorous Schreiber's Bent-winged bats in the caves of Northern Spain in 2002, its infectivity and pathogenicity remain unclear. We examined the seroprevalence of LLOV in potentially exposed Schreiber's Bent-winged bats ( n = 60), common serotine bats ( n = 10) as controls, and humans ( n = 22) using an immunoblot assay. We found antibodies against LLOV GP 2 in all of Schreiber's Bent-winged bats serum pools, but not in any of the common serotine bats and human pools tested. To confirm this seroreactivity, 52 serums were individually tested using Domain Programmable Arrays (DPA), a phage display based-system serology technique for profiling filovirus epitopes. A serological signature against different LLOV proteins was obtained in 19/52 samples tested (36.5%). The immunodominant response was in the majority specific to LLOV-unique epitopes, confirming that the serological response detected was to LLOV. To our knowledge, this is the first serological evidence of LLOV exposure in live captured Schreiber's Bent-winged bats, dissociating LLOV circulation as the cause of the previously reported die-offs.

Tools with predictive capabilities in regards of filovirus outbreaks are mainly anthropocentric and have disregarded the ecological dimension of the problem. Here we contribute to shift the current paradigm by studying the dynamics of the putative main zoonotic niche of filoviruses, bats, and its link to environmental drivers. We propose a framework that combines data analysis, modeling, and the evaluation of sources of variability. We implement a regression analysis using factual data to correlate environmental parameters and the presence of bats to find the distribution of resources. The information inferred by the regression is fed into a compartmental model that describes the infection state. We also account for the lack of knowledge of some parameters using a sampling/averaging technique. As a result we estimate the spatio-temporal densities of bats. Importantly, we show that our approach is able to predict where and when an outbreak is likely to appear when tested against recent epidemic data in the context of Ebola. Our framework highlights the importance of considering the feedback between the ecology and the environment in zoonotic models and sheds light on the mechanisms to propagate filoviruses geographically. We expect that our methodology can help to design prevention policies and be used as a predictive tool in the context of zoonotic diseases associated to filoviruses.

Introduction: During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients. Potential benefits and pitfalls of combination therapies for filoviruses will be discussed. Areas covered: Clinical trials of therapeutics targeting EBOV; clinical usage of therapeutics during recent EBOV outbreak; potential need for combination therapy; role of supportive care in treatment of Ebola virus disease (EVD). Expert commentary: In the absence of another large scale EBOV outbreak, the path to therapeutic product licensure in the United States of America (USA) would need to be via the FDA Animal Rule. However, human data may be needed to supplement animal data. The future of filovirus therapeutics may therefore benefit by establishing the ability to implement clinical trials in an outbreak setting in a timely fashion. Supportive care guidelines for filovirus infection should be defined and established as standard of care for treatment of EVD.

Genetically divergent filoviruses detected in Rousettus and Eonycteris spp. bats in China exhibited 61%-99% nt identity with reported filoviruses, based on partial replicase sequences, and they demonstrated lung tropism. Co-infection with 4 different filoviruses was found in 1 bat. These results demonstrate that fruit bats are key reservoirs of filoviruses.

Filoviruses can cause severe and often fatal disease in humans. To date, there have been 47 outbreaks resulting in more than 31,500 cases of human illness and over 13,200 reported deaths. Since their discovery, researchers from many scientific disciplines have worked to better understand the natural history of these deadly viruses. Citing original research wherever possible, this chapter reviews laboratory and field-based studies on filovirus ecology and summarizes efforts to identify where filoviruses persist in nature, how virus is transmitted to other animals and ultimately, what drivers cause spillover to human beings. Furthermore, this chapter discusses concepts on what constitutes a reservoir host and highlights challenges encountered while conducting research on filovirus ecology, particularly field-based investigations.

Eight viruses are currently assigned to the family Filoviridae Marburg virus, Sudan virus and, in particular, Ebola virus have received the most attention both by researchers and the public from 1967 to 2013. During this period, natural human filovirus disease outbreaks occurred sporadically in Equatorial Africa and, despite high case-fatality rates, never included more than several dozen to a few hundred infections per outbreak. Research emphasis shifted almost exclusively to Ebola virus in 2014, when this virus was identified as the cause of an outbreak that has thus far involved more than 28 646 people and caused more than 11 323 deaths in Western Africa. Consequently, major efforts are currently underway to develop licensed medical countermeasures against Ebola virus infection. However, the ecology of and mechanisms behind Ebola virus emergence are as little understood as they are for all other filoviruses. Consequently, the possibility of the future occurrence of a large disease outbreak caused by other less characterized filoviruses (i.e. Bundibugyo virus, Lloviu virus, Ravn virus, Reston virus and Taï Forest virus) is impossible to rule out. Yet, for many of these viruses, not even rudimentary research tools are available, let alone medical countermeasures. This review summarizes the current knowledge on these less well-characterized filoviruses., (Published by Oxford University Press on behalf of FEMS 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Fruit bats are suspected to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Using an enzyme-linked immunosorbent assay based on the viral glycoprotein antigens, we detected filovirus-specific immunoglobulin G antibodies in 71 of 748 serum samples collected from migratory fruit bats (Eidolon helvum) in Zambia during 2006-2013. Although antibodies to African filoviruses (eg, Zaire ebolavirus) were most prevalent, some serum samples showed distinct specificity for Reston ebolavirus, which that has thus far been found only in Asia. Interestingly, the transition of filovirus species causing outbreaks in Central and West Africa during 2005-2014 seemed to be synchronized with the change of the serologically dominant virus species in these bats. These data suggest the introduction of multiple species of filoviruses in the migratory bat population and point to the need for continued surveillance of filovirus infection of wild animals in sub-Saharan Africa, including hitherto nonendemic countries., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Personal protective equipment (PPE) is an important part of worker protection during filovirus outbreaks. The need to protect against a highly virulent fluid-borne pathogen in the tropical environment imposes a heat stress on the wearer that is itself a safety risk. No evidence supports the choice of PPE employed in recent outbreaks, and standard testing procedures employed by the protective garment industry do not well simulate filovirus exposure. Further research is needed to determine the appropriate PPE for filoviruses and the heat stress that it imposes., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in comparison, the seven other known filovirus family members are significantly understudied. Many of these, including Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and fully capable of causing widespread epidemics. This review places the focus on these non-EBOV filoviruses, including known immunological and pathological data. The available animal models, research tools and currently available therapeutics will also be discussed along with an emphasis in the large number of current gaps in knowledge of these less highlighted filoviruses. It is evident that much research is yet to be done in order to bring the non-EBOV filovirus field to the forefront of current research and, importantly, to the development of more effective vaccines and therapeutics to combat potential future outbreaks.

Filoviruses are responsible for highly lethal infections. Those viruses are found in intertropical areas of Africa and Asia where they circulate in their supposed natural reservoir, fruit bats. During filovirus outbreaks and depending on the strains, various modifications in hemostasis have been observed in patients. The disseminated intravascular coagulation identified in these infections is multicausal and involves both viral factors and abnormal physiological responses. In this review we will describe the mechanisms responsible for these disturbances and we will highlight some aspects of the basis of filovirus high pathogenicity., (© 2015 médecine/sciences – Inserm.)

More than 1 240 species of bats are known; many of them are insectivorous, others are frugivorous and some american species are haematophagous. More than 100 diferent viruses are associated with these mammals, particularly Rhabdoviridae (Lyssavirus like rabies virus), Paramyxoviridae (like Nipah and Hendra viruses), Filoviridae (Ebola and Marburg viruses) and Coronavirida (viruses causing SARS and MERS). These infections are usually asymptomatic in bats but the mechanism of this tolerance is not yet understood. For those viruses, bats are efficient reservoirs and disseminators. So, they represent a significative risk for human and animal public health, that justifies to set up surveillance of bat-associated viruses and research programs about the particular immunity mechanisms of bats.

Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.

Filoviruses, including Ebolavirus and Marburgvirus, pose significant threats to public health and species conservation by causing hemorrhagic fever outbreaks with high mortality rates. Since the first outbreak in 1967, their origins, natural history, and ecology remained elusive until recent studies linked them through molecular, serological, and virological studies to bats. We review the ecology, epidemiology, and natural history of these systems, drawing on examples from other bat-borne zoonoses, and highlight key areas for future research. We compare and contrast results from ecological and virological studies of bats and filoviruses with those of other systems. We also highlight how advanced methods, such as more recent serological assays, can be interlinked with flexible statistical methods and experimental studies to inform the field studies necessary to understand filovirus persistence in wildlife populations and cross-species transmission leading to outbreaks. We highlight the need for a more unified, global surveillance strategy for filoviruses in wildlife, and advocate for more integrated, multi-disciplinary approaches to understand dynamics in bat populations to ultimately mitigate or prevent potentially devastating disease outbreaks.

In 2012, an unprecedented number of four distinct, partially overlapping filovirus-associated viral hemorrhagic fever outbreaks were detected in equatorial Africa. Analysis of complete virus genome sequences confirmed the reemergence of Sudan virus and Marburg virus in Uganda, and the first emergence of Bundibugyo virus in the Democratic Republic of the Congo., (Published by Elsevier Inc.)

Filovirus infection presents many unique challenges to patient management. Currently no approved treatments are available, and the recommendations for supportive care are not evidence based. The austere clinical settings in which patients often present and the sporadic and at times explosive nature of filovirus outbreaks have effectively limited the information available to evaluate potential management strategies. This review will summarize the management approaches used in filovirus outbreaks and provide recommendations for collecting the information necessary for evaluating and potentially improving patient outcomes in the future.

Testing an innovative therapy for filovirus hemorrhagic fever (FHF) in an outbreak setting may be years away. Moreover, beyond anecdotal evidence, little is known about best practice for outbreak case management. Currently, Médecins Sans Frontières and others provide FHF patients with basic supportive treatment. We describe and discuss treatment possibilities, challenges, and potential next steps for FHF outbreak case management. More comprehensive supportive treatment, including vital sign monitoring, intensive care components, and goal-directed interventions may contribute to improved clinical outcome; the feasibility and effectiveness of this more comprehensive supportive treatment should be assessed. Our outlined summary may assist future FHF outbreak case management teams to create collaborative platforms and develop relevant treatment protocols aimed at improving clinical outcome.

Understanding the ability to survive in an aerosol leads to better understanding of the hazard posed by pathogenic organisms and can inform decisions related to the control and management of disease outbreaks. This basic survival information is sometimes lacking for high priority select agents such as the filoviruses which cause severe disease with high case fatality rates and can be acquired through the aerosol route. Microthreads in the form of spiders' webs were used to capture aerosolised filoviruses, and the decay rates of Zaire ebolavirus and Marburgvirus were determined. Results were compared to data obtained using a Goldberg drum to measure survival as a dynamic aerosol. The two methods of obtaining aerostability information are compared., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Recent case reports of viral hemorrhagic fever in Europe and the United States have raised concerns about the possibility for increased importation of filoviruses to non-endemic areas. This emerging threat is concerning because of the increase in global air travel and the rise of tourism in central and eastern Africa and the greater dispersion of military troops to areas of infectious disease outbreaks. Marburg viruses (MARV) and Ebola viruses (EBOV) have been associated with outbreaks of severe hemorrhagic fever involving high mortality (25-90% case fatality rates). First recognized in 1967 and 1976 respectively, subtypes of MARV and EBOV are the only known viruses of the Filoviridae family, and are among the world's most virulent pathogens. This article focuses on information relevant for health care practitioners in travel medicine to include, the epidemiology and clinical features of filovirus infection and efforts toward development of a filovirus vaccine., (Published by Elsevier Ltd.)

Since the discovery of the Marburg and Ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. Domestic swine in the Philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host Reston ebolavirus (REBOV). Although REBOV is the only member of Filoviridae that has not been associated with disease in humans, its emergence in the human food chain is of concern. REBOV isolates were found to be more divergent from each other than from the original virus isolated in 1989, indicating polyphyletic origins and that REBOV has been circulating since, and possibly before, the initial discovery of REBOV in monkeys.

Filoviruses are zoonotic and among the deadliest viruses known to mankind, with mortality rates in outbreaks reaching up to 90%. Despite numerous efforts to identify the host reservoir(s), the transmission cycle of filoviruses between the animal host(s) and humans remains unclear. The last decade has witnessed an increase in filovirus outbreaks with a changing epidemiology. The high mortality rates and lack of effective antiviral drugs or preventive vaccines has propagated the fear that filoviruses may become a real pandemic threat. This article discusses the factors that could influence the possible pandemic potential of filoviruses and elaborates on the prerequisites for the containment of future outbreaks, which would help prevent the evolution of filovirus into more virulent and more transmissible viruses.

Significant progress has been made in vaccine development against infection by Ebola and Marburg viruses, members of the Filoviridae, which cause severe hemorrhagic fevers in humans with no effective treatment and a mortality rate of up to 90%. Several vaccine strategies have been shown to effectively protect immunized animals against filovirus infection. Among these candidate vaccine strategies, virus-like particles represent a promising approach and have been shown to protect small laboratory animals as well as nonhuman primates against lethal challenge by Ebola and/or Marburg viruses. This review briefly summarizes filovirus epidemiology and pathogenesis, and focuses on the discussion of recent advances in filovirus vaccine development and the current understanding of protective immune responses against filovirus infection with an emphasis on the progress and challenge of filovirus virus-like particle vaccine development.

In the 40 years since the recognition of filoviruses as agents of lethal human disease, there have been no specific advances in antiviral therapies or vaccines and few clinical studies on the efficacy of supportive care. On 20 September 2006, experts from 14 countries representing 68 institutions integrally involved in the response to outbreaks of filovirus hemorrhagic fever gathered at the National Microbiology Laboratory of the Public Health Agency of Canada in Winnipeg to discuss possible remedies for this grim situation, in a unique workshop entitled "Marburg and Ebola Hemorrhagic Fever: Feasibility of Prophylaxis and Therapy." A summary of the opportunities for and challenges to improving treatment of filovirus hemorrhagic fevers is presented here.

Since Ebola fever emerged in Central Africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission from a hypothetical reservoir host(s) to humans. This research has comprised investigations on a variety of animals and their characterization as intermediate, incidental, amplifying, reservoir, or vector hosts. A viral transmission chain was recently unveiled after a long absence of epidemic Ebola fever. Animal trapping missions were carried out in the Central African rain forest in an area where several epidemics and epizootics had occurred between 2001 and 2005. Among the various animals captured and analyzed, three species of fruit bats (suborder Megachiroptera) were found asymptomatically and naturally infected with Ebola virus: Hypsignathus monstrosus (hammer-headed fruit beats), Epomops franqueti (singing fruit bats), and Myonycteris torquata (little collared fruit bats). From experimental data, serological studies and virus genetic analysis, these findings confirm the importance of these bat species as potential reservoir species of Ebola virus in Central Africa. While feeding bats drop partially eaten fruit and masticated fruit pulp (spats) to the ground, possibly promoting indirect transmission of Ebola virus to certain ground dwelling mammals, if virus is being shed in saliva by chronically and asymptomatically infected bats. Great apes and forest duikers are particularly sensitive to lethal Ebola virus infection. These terrestrial mammals feed on fallen fruits and possibly spats, suggesting a chain of events leading to Ebola virus spillover to these incidental hosts. This chain of events may occur sporadically at different sites and times depending on a combination of the phenology of fruit production by different trees, animal behavior, and various, but as yet still unknown environmental factors, which could include drought. During the reproductive period, infected body fluid can also be shed in the environment and present a potential risk for indirect transmission to other vertebrates.

The outbreak of Marburg haemorrhagic fever in Angola in 2004-2005 shows once again the devastating and rapid spread of viral haemorrhagic fevers in medical settings where hygiene practices are poorly applied or ignored. The legacy of years of war and poverty in Angola has resulted in very poor medical education and services. The initial high rate of infection among infants in Angola may have been related to poor hospital practices, possibly administration of vaccines. Though the outbreak in Angola was in a part of Africa not previously known to have filovirus infection, prior ecological modelling had predicted this location and many others. Prevention of future outbreaks will not be easy. The urgent need is dissemination of knowledge and the training, discipline and resources for good clinical practice. Educating the public to demand higher standards could be a powerful tool. Good practices are difficult to establish and maintain on the scale needed.

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.

We used ecologic niche modeling of outbreaks and sporadic cases of filovirus-associated hemorrhagic fever (HF) to provide a large-scale perspective on the geographic and ecologic distributions of Ebola and Marburg viruses. We predicted that filovirus would occur across the Afrotropics: Ebola HF in the humid rain forests of central and western Africa, and Marburg HF in the drier and more open areas of central and eastern Africa. Most of the predicted geographic extent of Ebola HF appear to have been observed; Marburg HF has the potential to occur farther south and east. Ecologic conditions appropriate for Ebola HF are also present in Southeast Asia and the Philippines, where Ebola Reston is hypothesized to be distributed. This first large-scale ecologic analysis provides a framework for a more informed search for taxa that could constitute the natural reservoir for this virus family.

Epidemiological issues, clinical course and laboratory diagnostics of Ebola haemorrhagic fever are reviewed. The structural features of virions and genetic variants of the virus are described along with ecology of Ebola virus. The data on Ebola fever global morbidity are also presented.

Objective: To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population., Participants: The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions., Evidence: MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed., Consensus Process: Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft., Conclusions: Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

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.

With the natural history of the filovirus family seemingly unknown, filovirus ecology in its natural environment remains a rudimentary field of research. In order to investigate the maintenance cycle of filovirus in Central Africa, a study was conducted within the rain forest of the Central African Republic. The epidemiological study determines the frequency and distribution of filovirus seroprevalence in a selected human population. Using an ELISA, serum samples from Pygmy and non-Pygmy populations were tested for Ebola-Zaire virus and Marburg (MBG) virus antibody. Filovirus antibody reacting sera were found in all zones investigated, and in all populations studied (Ebola virus IgG 5.3%; Marburg virus IgG 2.4%). Pygmies appeared to have a significantly higher seroprevalence (P < 0.03) against Ebola-Zaire virus (7.02%) than non-Pygmies (4.2%). MBG virus or related unknown filovirus strains also seem to be present in the western part of Central Africa. MBG virus antibodies were present in different Pygmy groups (ranging from 0.7 to 5.6%, mean 2.05%) and in several non-Pygmy populations (ranging from 0.0 to 3.9%, mean 3.4%) without an overall significant difference between the two groups (P = 0.14). The potentialities of nonpathogenic filovirus strains circulating in the Central African Republic are discussed.

Sensationalised accounts of wards of dying patients have fueled intense public fascination with filoviruses and highlighted the global threat of emerging and re-emerging infectious diseases. Filoviruses are the prototypical emerging pathogens: they cause a haemorrhagic disease of high case-fatality associated with explosive outbreaks due to person-to-person transmission, have no known treatment, occur unpredictably, and have an unknown reservoir. In truth, since their initial discovery in 1967, only a handful of filoviral outbreaks have occurred, mostly in remote locations. However, the documented occurrence of secondary cases in locations far from endemic areas validates the concern that filoviruses have the potential to cause unprecedented outbreaks in the future.

Filoviruses are causative agents of a hemorrhagic fever in man with mortalities ranging from 22 to 88%. They are enveloped, nonsegmented negative-stranded RNA viruses and are separated into two types, Marburg and Ebola, which can be serologically, biochemically and genetically distinguished. In general, there is little genetic variability among viruses belonging to the Marburg type. The Ebola type, however, is subdivided into at least three distinct subtypes. Marburg virus was first isolated during an outbreak in Europe in 1967. Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. The reemergence of Ebola, subtype Zaire, in Kikwit 1995 caused a worldwide sensation, since it struck after a sensibilization on the danger of Ebola virus disease. Person-to-person transmission by intimate contact is the main route of infection, but transmission by droplets and small aerosols among infected individuals is discussed. The natural reservoir for filoviruses remains a mystery. Filoviruses are prime examples for emerging pathogens. Factors that may be involved in emergence are international commerce and travel, limited experience in diagnosis and case management, import of nonhuman primates, and the potential of filoviruses for rapid evolution.