Outbreak Of Hemorrhagic Fever Research Articles

Crimean-Congo hemorrhagic fever outbreak affecting healthcare workers in Pakistan: an urgent rising concern

Crimean-Congo hemorrhagic fever outbreak affecting healthcare workers in Pakistan: an urgent rising concern

Tanzania's first Marburg Viral Disease outbreak response: Describing the roles of FELTP graduates and residents.

Viral Haemorrhagic Fever Outbreak presents a significant public health threat, requiring a timely, robust, and well-coordinated response. This paper aims to describe the roles of the Tanzania Field Epidemiology and Laboratory Training Program (TFELTP) graduates and residents in responding to Tanzania's first Marburg Viral Disease (MVD) outbreak. We performed a secondary data analysis using a range of documents, such as rosters of deployed responders and the TFELTP graduate and resident database, to count and describe them. Additionally, we conducted an exploratory textual analysis of field deployment reports and outbreak situational reports to delineate the roles played by the residents and graduates within each response pillar. A total of 70 TFELTP graduates and residents from different regions were involved in supporting the response efforts. TFELTP graduates and residents actively participated in several interventions, including contact tracing and follow up, sensitising clinicians on surveillance tools such as standard case definitions, alert management, supporting the National and Kagera Regional Public Health Emergency Operations Centres, active case search, risk communication, and community engagement, coordination of logistics, passenger screening at points of entry, and conducting Infection Prevention and Control (IPC) assessments and orientations in 144 Health Facilities. The successes achieved and lessons learned from the MVD response lay a foundation for sustained investment in skilled workforce development. FELTP Training is a key strategy for enhancing global health security and strengthening outbreak response capabilities in Tanzania and beyond.

Human macrophages infected with Egyptian Rousette bat-isolated Marburg virus display inter-individual susceptibility and antiviral responsiveness

Marburg virus (MARV) is a highly pathogenic filovirus and a causative agent of sporadic zoonotic viral hemorrhagic fever outbreaks with high case fatality rates. In humans, filoviruses like MARV and Zaire Ebola virus (EBOV) target, among others, innate immune cells like dendritic cells and macrophages (MΦs). Filovirus-infected dendritic cells display impaired maturation and antigen presentation, while MΦs become hyper-activated and secrete proinflammatory cytokines and chemokines. Our current understanding of human macrophage responses to MARV remains limited. Here, we used human monocyte-derived macrophages (moMΦs) to address how their phenotype, transcriptional profile, and protein expression change upon an in vitro infection with a bat isolate of MARV. Confirming its tropism for macrophages, we show that MARV induces notable shifts in their transcription distinct from responses induced by lipopolysaccharide (LPS), marked by upregulated gene expression of several chemokines, type I interferons, and IFN-stimulated genes. MARV infection also elicited pronounced inter-individually different transcriptional programs in moMΦs, the induction of Wnt signaling-associated genes, and the downregulation of multiple biological processes and molecular pathways.

Relation between the Pandemic COVID-19 and the outbreak of Crimean-Congo Hemorrhagic Fever in Iraq, 2023

Objective: This review examines the link between the COVID-19 pandemic and the outbreak of Crimean-Congo Hemorrhagic Fever (CCHF) in Iraq. Methods: We reviewed literature and data to explore potential associations between the two diseases. Results: No direct causative link between COVID-19 and increased CCHF cases in Iraq was found. However, changes in healthcare,agriculture, and human-animal interactions during the pandemic may have indirectly affected CCHF transmission. Conclusion: This review highlights the need for further research to confirm any connections between the COVID-19 pandemic and CCHFoutbreaks in Iraq. Understanding these links is crucial for effective public health responses to emerging infectious diseases.

Assessment of the integrated disease surveillance and response system implementation in health zones at risk for viral hemorrhagic fever outbreaks in North Kivu, Democratic Republic of the Congo, following a major Ebola outbreak, 2021

BackgroundThe Democratic Republic of the Congo (DRC) experienced its largest Ebola Virus Disease Outbreak in 2018–2020. As a result of the outbreak, significant funding and international support were provided to Eastern DRC to improve disease surveillance. The Integrated Disease Surveillance and Response (IDSR) strategy has been used in the DRC as a framework to strengthen public health surveillance, and full implementation could be critical as the DRC continues to face threats of various epidemic-prone diseases. In 2021, the DRC initiated an IDSR assessment in North Kivu province to assess the capabilities of the public health system to detect and respond to new public health threats.MethodsThe study utilized a mixed-methods design consisting of quantitative and qualitative methods. Quantitative assessment of the performance in IDSR core functions was conducted at multiple levels of the tiered health system through a standardized questionnaire and analysis of health data. Qualitative data were also collected through observations, focus groups and open-ended questions. Data were collected at the North Kivu provincial public health office, five health zones, 66 healthcare facilities, and from community health workers in 15 health areas.ResultsThirty-six percent of health facilities had no case definition documents and 53% had no blank case reporting forms, limiting identification and reporting. Data completeness and timeliness among health facilities were 53% and 75% overall but varied widely by health zone. While these indicators seemingly improved at the health zone level at 100% and 97% respectively, the health facility data feeding into the reporting structure were inconsistent. The use of electronic Integrated Disease Surveillance and Response is not widely implemented. Rapid response teams were generally available, but functionality was low with lack of guidance documents and long response times.ConclusionSupport is needed at the lower levels of the public health system and to address specific zones with low performance. Limitations in materials, resources for communication and transportation, and workforce training continue to be challenges. This assessment highlights the need to move from outbreak-focused support and funding to building systems that can improve the long-term functionality of the routine disease surveillance system.

Crimean‐Congo haemorrhagic fever outbreak in Northern Senegal in 2022: Prevalence of the virus in livestock and ticks, associated risk factors and epidemiological implications

Crimean‐Congo haemorrhagic fever outbreak in Northern Senegal in 2022: Prevalence of the virus in livestock and ticks, associated risk factors and epidemiological implications

Crimean-Congo Hemorrhagic Fever Virus Diversity and Reassortment, Pakistan, 2017-2020.

Sporadic cases and outbreaks of Crimean-Congo hemorrhagic fever (CCHF) have been documented across Pakistan since 1976; however, data regarding the diversity of CCHF virus (CCHFV) in Pakistan is sparse. We whole-genome sequenced 36 CCHFV samples collected from persons infected in Pakistan during 2017-2020. Most CCHF cases were from Rawalpindi (n = 10), followed by Peshawar (n = 7) and Islamabad (n = 4). Phylogenetic analysis revealed the Asia-1 genotype was dominant, but 4 reassorted strains were identified. Strains with reassorted medium gene segments clustered with Asia-2 (n = 2) and Africa-2 (n = 1) genotypes; small segment reassortments clustered with the Asia-2 genotype (n = 2). Reassorted viruses showed close identity with isolates from India, Iran, and Tajikistan, suggesting potential crossborder movement of CCHFV. Improved and continuous human, tick, and animal surveillance is needed to define the diversity of circulating CCHFV strains in Pakistan and prevent transmission.

Seroprevalence of Bas-Congo virus in Mangala, Democratic Republic of the Congo: a population-based cross-sectional study

Bas-Congo virus (BASV), an emerging tibrovirus, was associated with an outbreak of acute haemorrhagic fever in Mangala, Democratic Republic of the Congo, in 2009. In 2012, neutralising antibodies to BASV were detected in the lone survivor and one of his close contacts. However, subsequent serological and molecular surveys were unsuccessful as neither BASV antibodies nor its RNA were detected. In this study, we determined the seroprevalence of BASV infection in Mangala 13 years after the initial outbreak. We conducted a population-based serological survey from Jan 17 to Jan 23, 2022. Consenting individuals at least 5 years of age, living in Mangala for at least 4 weeks, and who had no contraindication to venepuncture were enrolled. Participants were interviewed using a pre-tested questionnaire for sociodemographic and clinical characteristics. We supplemented the collected serum samples with 284 archived samples from Matadi and Kinshasa. All samples were tested for antibodies to BASV and other tibroviruses using a pseudovirus-based neutralisation test. Among the 267 individuals from Mangala, the prevalence of BASV antibodies was 55% (95% CI 49-61; n=147). BASV seropositivity odds significantly increased with age (5·2 [95% CI 2·1-12·9] to 83·9 [20·8-337·7] times higher in participants aged 20 years or older than participants aged 5-19 years). Some occupational categories (eg,farmer or public servant) were associated with seropositivity. Only nine (6%) of 160 samples from Matadi and one (<1%) of 124 samples from Kinshasa had neutralising antibodies to BASV. Moreover, we also detected neutralising antibodies to other tibroviruses-Ekpoma virus 1, Ekpoma virus 2, and Mundri virus-in 84 (31%), 251 (94%), and 219 (82%) of 267 Mangala samples; 14 (9%), 62 (39%), and 120 (75%) of 160 Matadi samples; and six (5%), five (4%), and 33 (27%) of 124 Kinshasa samples, respectively. Human infection with BASV and other tibroviruses seems common in Mangala, although no deadly outbreak has been reported since 2009. Exposure to BASV might be highly restricted to Mangala and the increasing prevalence of neutralising antibodies with age suggests regular contact with the virus in this city. Altogether, our findings suggest that human infection with tibroviruses could be common in the study areas and not associated with deadly haemorrhagic or debilitating syndromes. Japan Agency for Medical Research and Development (AMED) and Japan International Cooperation Agency (JICA) under the Science and Technology Research Partnership for Sustainable Development (SATREPS) and Japan Program for Infectious Diseases Research and Infrastructure from AMED.

Epidemic survey of Crimean-Congo hemorrhagic fever infections in the Iraqi population during 2022

The primary cause of the Crimean-Congo hemorrhagic fever (CCHF) is a virus spread by ticks. The rate of frequency of case mortality is 10–40%, which is spurred on by the CCHF virus, which also produces severe viral hemorrhagic fever outbreaks. The current study can be viewed as an epidemiological survey of CCHF infections in Iraq, with the goal of better understanding block virus transmission and preventing the risk of contracting the disease. Approximately 1370 blood samples from suspect patients were taken and separated; then, the serum was processed to remove viral RNA and tested for CCHF infection using specialized kits. Results revealed 382 (27.9%) positive cases, including 76 (19.9%) positive patients with dying compared to 306 (80.1%) who experienced cures. Findings showed a significant incidence of more than 50% of the positive cases having contact with animals and raw meat, 33% slaughtering, and 36% tick bites. Furthermore, 125 (32.7%) homemakers and 64 (16.8%) butchers had the most significant infection percentage. With 42.4% of all infections, Thiqar province had the most infected patients, followed by Misan with 9.7%, then Wasit and Babil. With 27.2% of all infections, May had the most CCHF-positive infections, followed by June and July. In conclusion, in response to the initial wave counterattack in southern Iraq, public health interventions on the veterinarian side should be implemented; these should eliminate, or at least decrease, the impact of a second wave. Illegal trading practices must be controlled if zoonotic diseases like CCHF are to stop spreading. Keywords: CCHF, Iraqi provinces, RT-PCR, tick bites, zoonotic disease.

The Outbreak of Crimean-Congo hemorrhagic fever (CCHF) in Al-Hsseiniya District /Karbala province in Iraq: A control strategy

The Outbreak of Crimean-Congo hemorrhagic fever (CCHF) in Al-Hsseiniya District /Karbala province in Iraq: A control strategy

Epidemiological study of the 2023 Crimean-Congo hemorrhagic fever outbreak in Iraq

ObjectivesCrimean-Congo hemorrhagic fever (CCHF) is a tick-borne virus disease that is of a high concern for global health care systems because there is no specific treatment or vaccination available for it yet. The disease is endemic in several countries around the world and humans can get infected with the virus through the tick bites or by coming into contact with tissues or blood of the infected animals. This study aimed to describe the epidemiology of the disease in Iraq from January 1, 2023 to June 18, 2023. MethodsThis is a retrospective study and the epidemiological data of CCHF in Iraq within the first 6 months of 2023 were kindly provided by the Sulaymaniyah directory of the World Health Organization/Iraq. ResultsOverall, 229 CCHF cases and 36 deaths were recorded during this study. The majority of the cases were aged between 15 and 45 years, and the gender distribution ratio of males to females was 61% and 39%, respectively. ConclusionsCCHF is an extremely severe disease that poses a threat to the public health. The hyper-endemic status of CCHF in Iraq is continuing and the number of cases has increased in 2023 compared with 2022.

Another Crimean-Congo hemorrhagic fever outbreak in Uganda: Ongoing challenges with prevention, detection, and response

ObjectivesTo highlight the challenges associated with Crimean-Congo hemorrhagic fever (CCHF) prevention, detection, and response in Uganda. MethodsWe describe a single confirmed CCHF case in Rakai District in 2022. We reviewed medical records and conducted interviews on the case patient’s history and possible exposures. To understand CCHF prevention and response efforts, we conducted key informant interviews with the district health and veterinary officers and focus group discussions with farmers in the affected village. ResultsAn 18-year-old Rakai District resident had fever onset on July 5, 2022. Despite hemorrhaging during hospital admission on July 6, a viral hemorrhagic fever was not suspected for 24 h and appropriate personal protective equipment was not used. A blood sample was collected for viral hemorrhagic fever testing on July 8; however, the patient was discharged before receiving results. The case patient tested positive for CCHF on July 12 and was readmitted. Key informant interviews and focus group discussions indicated poor tick control measures in the district. The district lacked a formal One Health team and experienced challenges with coordination for outbreak response. ConclusionsCCHF prevention, detection, and response face challenges in Uganda and require strong clinical awareness for quick detection, collaboration between animal and human health stakeholders, and implementation of effective tick control measures.

Novel Oliveros-like Clade C Mammarenaviruses from Rodents in Argentina, 1990-2020.

Following an Argentine Hemorrhagic Fever (AHF) outbreak in the early 1990s, a rodent survey for Junín virus, a New World Clade B arenavirus, in endemic areas of Argentina was conducted. Since 1990, INEVH has been developing eco-epidemiological surveillance of rodents, inside and outside the Argentine Hemorrhagic Fever endemic area. Samples from rodents captured between 1993 and 2019 that were positive for Arenavirus infection underwent Sanger and unbiased, Illumina-based high-throughput sequencing, which yielded 5 complete and 88 partial Mammarenaviruses genomes. Previously, 11 genomes representing four species of New World arenavirus Clade C existed in public records. This work has generated 13 novel genomes, expanding the New World arenavirus Clade C to 24 total genomes. Additionally, two genomes exhibit sufficient genetic diversity to be considered a new species, as per ICTV guidelines (proposed name Mammarenavirus vellosense). The 13 novel genomes exhibited reassortment between the small and large segments in New World Mammarenaviruses. This work demonstrates that Clade C Mammarenavirus infections circulate broadly among Necromys species in the Argentine Hemorrhagic Fever endemic area; however, the risk for Clade C Mammarenavirus human infection is currently unknown.

The 2022 Crimean-Congo Hemorrhagic Fever outbreak in Iraq

Crimean-Congo Hemorrhagic fever (CCHF) is an endemic, zoonotic, viral, and tick-borne disease that causes hemorrhagic symptoms. The disease has been reported in Iraq since 1979 comprising six cases between 1989 and 2009. Subsequently, 11, 3, and 33 cases were reported in 2010, 2018, and 2021, respectively. This study describes the 2022 Crimean-Congo Hemorrhagic fever virus (CCHFV) outbreak in different Iraqi governorates. In the 2022 outbreak, 212 cases of human CCHFV were reported between January 1 and May 22. These included 97 (46%) cases confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and 115 (54%) suspected cases. Most human cases have been reported for livestock breeders and butchers. Approximately half of the confirmed cases (48%) were reported in the Dhi Qar governorate, whereas the others were reported in Missan, Muthanna, Wasit, Diwaniya, Karkh/Baghdad, Rusafa/Baghdad, Kirkuk, Basra, Najaf, Nineveh, Babylon, and Karbala. Patients with CCHFV showed symptoms of the pre-hemorrhagic phase, including sudden fever, anorexia, vomiting, diarrhea, headache, nose bleeding, and abdominal and joint pain. Later, hemorrhagic symptoms started with unexplained bleeding lesions, ranging from small petechiae to large hematomas. The factors responsible for the re-emergence of CCHFV included a shortage of veterinary services during the COVID-19 pandemic and illegal slaughtering of animals outside the abattoirs. This led to massive tick infestations that acted as viral vectors. In conclusion, this is the first report documenting the 2022 CCHFV outbreak in Iraq, with a total of 212 patients and 27 overall deaths, including 13 laboratory-confirmed cases. The authors recommend improving veterinary services provided to farmers. Additionally, future studies need to be done including the sero-epidemiology and molecular studies on local livestock and ticks to understand their roles in circulating the virus to humans.

New Research Studies Future Treatments on Marburg Virus

Marburg virus disease (MVD), formerly known as Marburg haemorrhagic fever, is a severe, often fatal illness in humans. The virus causes severe viral haemorrhagic fever in humans. The identification of the natural reservoir of this virus should also foster the development health measures and prevention campaigns to the population to reduce the apparition and emergence of potential outbreaks of hemorrhagic fever. The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine “MARVAC” consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. While much is being investigated to devise a vaccine, it is important to educate Health Care Workers (HCWs) and close contacts facing the illness

ASFV antigens selected from genotype I immunised pigs are immunogenic, but do not protect against genotype II challenge.

African swine fever virus (ASFV) has recent caused outbreaks of viral haemorrhagic fever in domestic pigs and wild boar in Africa, Asia, Europe, Oceania and North America. Control measures for African swine fever are limited in most countries to biosecurity at the farm gate followed by movement restrictions and selective or complete culling of pigs on affected premises. Modified live vaccines are being trialled in several countries, however development of safe and effective African swine fever subunit vaccines has been restricted by a poor understanding of the key antigens required for protection, particularly for the panzootic genotype II viruses. The cellular immune response is thought to be critical for protection against African swine fever and therefore to develop an effective subunit vaccine that stimulates an anti-ASFV T-cell response we screened lymphocytes from pigs which survived challenge with Georgia 2007/1. Using an overlapping peptide library corresponding to 168 annotated open reading frames and 24 potential minor open reading frames we identified seventeen proteins with strongly stimulated secretion of interferon gamma in an ELISpot assay. The phenotype of the T cells which were stimulated by these pools of peptides were then investigated by flow cytometry. Proteins stimulating predominantly CD8+ T cells were incorporated into bivalent replication deficient adenovirus vectors and tested as potential vaccine candidates in immunisation and challenge experiments in pigs.

2070. Outbreak of Crimean-Congo Hemorrhagic Fever in Kyzylorda region, Kazakhstan, March-July 2022

Abstract Background Crimean-Congo Hemorrhagic Fever (CCHF) is a viral tick-borne disease with a high mortality rate. It is endemic in Kazakhstan. The Kyzylorda region reported higher-than-expected cases from March to July 2022 (15 compared to 10 in the previous year). We conducted an investigation to identify additional cases, determine risk factors, and assess CCHF knowledge and practices. Methods We conducted a case-control study in July 2022. We defined cases as PCR-confirmed or hospitalized with CCHF symptoms. The control group was made up of regional contacts including neighbors and household members at a 1:2 ratio. We reviewed medical records from April to July. We conducted face-to-face interviews using structured questionnaires. Blood collected from the control group was tested with PCR and ELISA for detection of IgM and IgG antibodies. We also collected ticks from domestic animals for PCR-testing. We used logistic regression to assess factors associated with CCHF. Results We identified 38 cases (n=15 confirmed, n=7 probable and n=16 suspected cases) and 71 controls. Cases were mostly male (74%) with mean age of 45 (range 17-81); 27% died. Top patient symptoms (n=38) were weakness (100%), headache (97%), fever (84%) and loss of appetite (55%). Risk factors for CCHF were being male (odds ratio and 95% confidence interval: 5.5, CI: 2.3-13.1), animal husbandry (3.1, 1.3-7.2), crop production (4.0, 1.5-10.5), tick contact (262.5, CI: 31.4-2192.2), tick bite (70.0, 8.8-556.9), contact with tick blood (18.7, 2.2-155.9), ticks on the body or clothing (77.8, 9.8-618.9) and having been in places with high tick risk (15.1, CI: 4.6-49.7). The control group were more likely to have awareness of CCHF, know that they can protect themselves from CCHF, refrained from visiting forests and rural areas, used repellents, and taken protective measures to reduce ticks in domestic animals. Of 55 controls tested: one was IgG positive. Of 163 ticks tested, one was PCR-positive. Conclusion Exposure to activities that are high risk for exposure to ticks increased odds of CCHF. Improved awareness of prevention to exposure from ticks, CCHF associated risk factors, and the importance of seeking early treatment is needed. This can be achieved by increasing population awareness and educating medical providers. Disclosures All Authors: No reported disclosures

Alarming update on incidence of Crimean-Congo hemorrhagic fever in Iraq in 2023

ObjectivesIn 2021, large outbreak of Crimean-Congo hemorrhagic fever (CCHF) was reported in Iraq and cases have increased without any significant control measures. To raise awareness about the increasing cases in different regions of Iraq, hence remind the necessity to tackle contributing factors and potential outbreak interventions. MethodsThe study included 511 polymerase chain reaction-confirmed CCHF infection cases out of 1827 suspected cases from 18 Provinces from January to August 2023. Approval from the Ministry of Health for data analyzed. ResultsOut of 1827 suspected cases, 511 were confirmed positive by polymerase chain reaction. The total case fatality rate (CFR) was 12.7 with varying severity levels among provinces. Erbil had the highest CFR, 38.5, while Sulaimaniya and Anbar report no deaths. Independent t-test showed a significant difference in CFR between provinces west and south of Baghdad compared to north (P <0.05). Trend showed significant surges after Iftar and Adha holidays. ConclusionDifferences in CFR among provinces around the religious ceremonies, highlight the need for one public health intervention strategy. Increased temperatures affected vector behavior. Uncontrolled animal movement with neighboring countries is an important factor. Virus or host determinants can shape the clinical case outcomes, which need clinical and extensive laboratory studies to unravel the reasons leading to death.

Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein

Ebolaviruses, such as the highly pathogenic Ebola virus (EBOV), belong to the family Filoviridae and have caused outbreaks of severe and fatal hemorrhagic fever over the past years. Bombali virus (BOMV) is a newly discovered ebolavirus from bats with unknown potential to infect humans. For most ebolaviruses, the interaction between viral glycoprotein (GP) and host receptor Niemann-Pick C1 (NPC1) is crucial for viral entry and determines host tropism. Here, we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription- and replication-competent virus-like particle (trVLP) system. We demonstrated that while BOMV GP can be efficiently incorporated into trVLPs, it is inefficient in mediating trVLP entry into human cells. However, BOMV GP-mediated virus entry into human cells can be significantly enhanced by a few mutations in the NPC1-binding domain of GP. Furthermore, we showed that these mutations increase the binding of BOMV-GP to human NPC1. In summary, our results suggested that although wild-type BOMV does not efficiently infect human cells, the emergence of mutations in viral GP may boost its ability to spill over to humans, highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.

Extracellular vesicle storm during the course of Ebola virus infection in primates.

Ebola virus (EBOV) is an RNA virus of the Filoviridae family that is responsible for outbreaks of hemorrhagic fevers in primates with a lethality rate as high as 90%. EBOV primarily targets host macrophages leading to cell activation and systemic cytokine storm, and fatal infection is associated with an inhibited interferon response, and lymphopenia. The EBOV surface glycoprotein (GP) has been shown to directly induce T cell depletion and can be secreted outside the virion via extracellular vesicles (EVs), though most studies are limited to epithelial cells and underlying mechanisms remain poorly elucidated. To assess the role of GP on EBOV-induced dysregulation of host immunity, we first utilized EBOV virus-like particles (VLPs) expressing VP40 and NP either alone (Bald-VLP) or in conjunction with GP (VLP-GP) to investigate early inflammatory responses in THP-1 macrophages and in a murine model. We then sought to decipher the role of non-classical inflammatory mediators such as EVs over the course of EBOV infection in two EBOV-infected rhesus macaques by isolating and characterizing circulatory EVs throughout disease progression using size exclusion chromatography, nanoparticle tracking-analysis, and LC-MS/MS. While all VLPs could induce inflammatory mediators and recruit small peritoneal macrophages, pro-inflammatory cytokine and chemokine gene expression was exacerbated by the presence of GP. Further, quantification of EVs isolated from infected rhesus macaques revealed that the concentration of vesicles peaked in circulation at the terminal stage, at which time EBOV GP could be detected in host-derived exosomes. Moreover, comparative proteomics conducted across EV populations isolated from serum at various time points before and after infection revealed differences in host-derived protein content that were most significantly pronounced at the endpoint of infection, including significant expression of mediators of TLR4 signaling. These results suggest a dynamic role for EVs in the modification of disease states in the context of EBOV. Overall, our work highlights the importance of viral factors, such as the GP, and host derived EVs in the inflammatory cascade and pathogenesis of EBOV, which can be collectively further exploited for novel antiviral development.