ABSTRACT
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, I2 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).
Subject(s)
Filoviridae Infections , Systematic Reviews as Topic , Humans , Africa South of the Sahara/epidemiology , Prevalence , Filoviridae Infections/epidemiology , Meta-Analysis as Topic , Hemorrhagic Fever, Ebola/epidemiology , Animals , FiloviridaeABSTRACT
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.
Subject(s)
Antibodies, Viral/blood , Filoviridae Infections/immunology , Filoviridae Infections/veterinary , Filoviridae/immunology , Primates/virology , Animals , Animals, Wild/virology , Chlorocebus aethiops/virology , Ebolavirus/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Filoviridae/classification , Filoviridae/isolation & purification , Filoviridae Infections/epidemiology , Humans , Immunoglobulin G/blood , Male , Marburgvirus/immunology , Papio/virology , Seroepidemiologic Studies , Zambia/epidemiologyABSTRACT
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.
Subject(s)
Chiroptera/virology , Filoviridae Infections/veterinary , Filoviridae , Henipavirus Infections/veterinary , Henipavirus , Animals , Chiroptera/blood , Chiroptera/classification , Filoviridae Infections/epidemiology , Filoviridae Infections/virology , Henipavirus Infections/epidemiology , Henipavirus Infections/virology , Serologic Tests , Trinidad and Tobago/epidemiologyABSTRACT
A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary.
Subject(s)
Antibodies, Viral/blood , Filoviridae/immunology , Marburg Virus Disease/blood , Marburg Virus Disease/epidemiology , Marburgvirus/immunology , Animals , Cameroon/epidemiology , Enzyme-Linked Immunosorbent Assay , Filoviridae/genetics , Filoviridae Infections/blood , Filoviridae Infections/epidemiology , Filoviridae Infections/virology , Ghana/epidemiology , Humans , Marburg Virus Disease/virology , Marburgvirus/genetics , Retrospective Studies , Seroepidemiologic StudiesABSTRACT
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.
Subject(s)
Antibodies, Viral/blood , Chiroptera/immunology , Chiroptera/virology , Disease Reservoirs/virology , Filoviridae Infections/epidemiology , Filoviridae Infections/veterinary , Filoviridae/immunology , Adolescent , Adult , Animals , Chiroptera/blood , Ebolavirus/immunology , Filoviridae/classification , Filoviridae/isolation & purification , Filoviridae Infections/immunology , Filoviridae Infections/virology , Geographic Mapping , Glycoproteins/immunology , Humans , India/epidemiology , Membrane Glycoproteins , Middle Aged , Phylogeny , Seroepidemiologic Studies , Young AdultABSTRACT
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 GP2 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.
Subject(s)
Antibodies, Viral/blood , Chiroptera/virology , Filoviridae Infections/veterinary , Filoviridae/immunology , Viral Proteins/immunology , Animals , Cell Surface Display Techniques , Chiroptera/immunology , Female , Filoviridae Infections/epidemiology , Filoviridae Infections/immunology , Humans , Male , Prevalence , Seroepidemiologic Studies , Spain/epidemiologyABSTRACT
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.
Subject(s)
Chiroptera , Filoviridae Infections/epidemiology , Forecasting , Animals , Demography , Disease Outbreaks/statistics & numerical data , Disease Outbreaks/veterinary , Ebolavirus/isolation & purification , Ecology , Epidemics , Filoviridae Infections/diagnosis , Filoviridae Infections/prevention & control , Filoviridae Infections/veterinary , Forecasting/methods , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/veterinary , Humans , Population Forecast , Zoonoses/epidemiology , Zoonoses/prevention & controlSubject(s)
Chiroptera/virology , Communicable Diseases, Emerging/veterinary , Filoviridae Infections/veterinary , Filoviridae/isolation & purification , Animals , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Filoviridae/classification , Filoviridae/genetics , Filoviridae Infections/epidemiology , Filoviridae Infections/pathology , Filoviridae Infections/virology , Hungary/epidemiology , Lung/pathology , Lung/virology , PhylogenyABSTRACT
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.
Subject(s)
Antiviral Agents/therapeutic use , Disease Outbreaks , Hemorrhagic Fever, Ebola/drug therapy , Animals , Antiviral Agents/administration & dosage , Drug Approval , Drug Design , Drug Therapy, Combination , Ebolavirus/drug effects , Ebolavirus/isolation & purification , Filoviridae/drug effects , Filoviridae/isolation & purification , Filoviridae Infections/drug therapy , Filoviridae Infections/epidemiology , Hemorrhagic Fever, Ebola/epidemiology , HumansABSTRACT
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.
Subject(s)
Ecology , Filoviridae Infections/transmission , Filoviridae Infections/virology , Filoviridae , Animals , Disease Outbreaks , Filoviridae/isolation & purification , Filoviridae/pathogenicity , Filoviridae Infections/epidemiology , HumansABSTRACT
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.
Subject(s)
Chiroptera/virology , Filoviridae Infections/veterinary , Filoviridae/genetics , Genetic Variation , Animals , China/epidemiology , Filoviridae/isolation & purification , Filoviridae Infections/epidemiology , Filoviridae Infections/virology , HumansABSTRACT
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.
Subject(s)
Communicable Diseases, Emerging/virology , Filoviridae Infections/virology , Neglected Diseases/virology , Africa/epidemiology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Disease Outbreaks/prevention & control , Filoviridae , Filoviridae Infections/epidemiology , Filoviridae Infections/prevention & control , Humans , Neglected Diseases/epidemiology , Neglected Diseases/prevention & controlABSTRACT
Filoviruses (Ebola and Marburg) are highly contagious pathogens, which cause severe and often fatal illness in humans. Health workers are at increased risk of infection with these viruses because of their close and prolonged contact with severely ill patients with a high viral load. The risk of transmission of Ebola virus can be reduced if appropriate measures are taken, including the use of personal protective equipment (PPE). The urgent need for clear standards for PPE use became acutely apparent during the unprecedented outbreak of Ebola virus disease (EVD) in certain western African countries in 201316.
Subject(s)
Humans , Health Personnel/education , Filoviridae Infections/prevention & control , Personal Protective Equipment/standards , Filoviridae Infections/epidemiology , Africa, Western/epidemiologyABSTRACT
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.
Subject(s)
Filoviridae Infections/epidemiology , Filoviridae Infections/virology , Filoviridae/physiology , Animals , Biomedical Research/trends , Disease Models, Animal , Disease Outbreaks , Filoviridae/immunology , Filoviridae/pathogenicity , Filoviridae Infections/immunology , Filoviridae Infections/pathology , Humans , VirulenceABSTRACT
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.
Subject(s)
Disseminated Intravascular Coagulation/etiology , Filoviridae Infections/blood , Adrenal Cortex/pathology , Animals , Chiroptera/virology , Communicable Diseases, Emerging/blood , Communicable Diseases, Emerging/complications , Cytokines/metabolism , Disease Reservoirs , Endothelial Cells/pathology , Filoviridae/physiology , Filoviridae Infections/epidemiology , Filoviridae Infections/pathology , Filoviridae Infections/veterinary , Filoviridae Infections/virology , Haplorhini , Hepatocytes/pathology , Host-Pathogen Interactions , Humans , Necrosis , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Thromboplastin/antagonists & inhibitors , Thromboplastin/physiology , Viral Load , Viral Proteins/physiologyABSTRACT
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.