Research

15 pages, 2016 KiB

Open AccessArticle

Establishing Healthcare Worker Performance and Safety in Providing Critical Care for Patients in a Simulated Ebola Treatment Unit: Non-Randomized Pilot Study

by Peter Kiiza, Sarah I. Mullin, Koren Teo, Len Goodman, Adic Perez, Ruxandra Pinto, Kelly Thompson, Dominique Piquette, Trevor Hall, Elhadj I. Bah, Michael Christian, Jan J. Hajek, Raymond Kao, François Lamontagne, John C. Marshall, Sharmistha Mishra, Srinivas Murthy, Abel Vanderschuren, Robert A. Fowler and Neill K. J. Adhikari

Viruses 2021, 13(11), 2205; https://doi.org/10.3390/v13112205 - 02 Nov 2021

Cited by 1 | Viewed by 2196

Abstract

Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 [...] Read more.

Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 °C, 60% relative humidity) or thermo-neutral (20 °C, 20% relative humidity) conditions. In this pilot phase to determine the feasibility of study procedures, HCWs in PPE were non-randomly allocated to hot or thermo-neutral conditions to perform peripheral intravenous (PIV) and midline catheter (MLC) insertion and endotracheal intubation (ETI) on mannequins. Eighteen HCWs (13 physicians, 4 nurses, 1 nurse practitioner; 2 with prior ETU experience; 10 in hot conditions) spent 69 (10) (mean (SD)) minutes in the simulated ETU. Mean (SD) task completion times were 16 (6) min for PIV insertion; 33 (5) min for MLC insertion; and 16 (8) min for ETI. Satisfactory task completion was numerically higher for physicians vs. nurses. Participants’ blood pressure was similar, but heart rate was higher (p = 0.0005) post-simulation vs. baseline. Participants had a median (range) of 2.0 (0.0–10.0) minor PPE breaches, 2.0 (0.0–6.0) near-miss incidents, and 2.0 (0.0–6.0) health symptoms and concerns. There were eight health-assessment triggers in five participants, of whom four were in hot conditions. We terminated the simulation of two participants in hot conditions due to thermal discomfort. In summary, study tasks were suitable for physician participants, but they require redesign to match nurses’ expertise for the subsequent randomized phase of the study. One-quarter of participants had a health-assessment trigger. This research model may be useful in future training and research regarding clinical care for patients with highly infectious pathogens in austere settings. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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8 pages, 1548 KiB

Open AccessArticle

Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment

by Daniel S. Chertow, Louis Shekhtman, Yoav Lurie, Richard T. Davey, Theo Heller and Harel Dahari

Viruses 2020, 12(1), 106; https://doi.org/10.3390/v12010106 - 16 Jan 2020

Cited by 6 | Viewed by 3391

Abstract

Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and [...] Read more.

Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and tissues throughout the body. Current in-host mathematical models simplify EBOV infection by assuming a single homogeneous compartment of infection. In particular, a recent modeling study assumed the liver as the largest solid organ targeted by EBOV infection and predicted that nearly all cells become refractory to infection within seven days of initial infection without antiviral treatment. We compared our observations of EBOV kinetics in multiple anatomic compartments and hepatocellular injury in a critically ill patient with Ebola virus disease (EVD) with this model’s predictions. We also explored the model’s predictions, with and without antiviral therapy, by recapitulating the model using published inputs and assumptions. Our findings highlight the challenges of modeling EBOV–host dynamics and therapeutic efficacy and emphasize the need for iterative interdisciplinary efforts to refine mathematical models that might advance understanding of EVD pathogenesis and treatment. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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29 pages, 5880 KiB

Open AccessArticle

Characterization of Ebola Virus Disease (EVD) in Rhesus Monkeys for Development of EVD Therapeutics

by Travis Warren, Elizabeth Zumbrun, Jessica M. Weidner, Laura Gomba, Franco Rossi, Roy Bannister, Jacqueline Tarrant, Matthew Reed, Eric Lee, Jo Lynne Raymond, Jay Wells, Joshua Shamblin, Kelly Wetzel, Ginger Donnelly, Sean Van Tongeren, Nicole Lackemeyer, Jesse Steffens, Adrienne Kimmel, Carly Garvey, Holly Bloomfield, Christiana Blair, Bali Singh, Sina Bavari, Tomas Cihlar and Danielle Porter Show full author list Hide full author list

Viruses 2020, 12(1), 92; https://doi.org/10.3390/v12010092 - 13 Jan 2020

Cited by 16 | Viewed by 3840

Abstract

Recent Ebola virus (EBOV) outbreaks in West Africa and the Democratic Republic of the Congo have highlighted the urgent need for approval of medical countermeasures for treatment and prevention of EBOV disease (EVD). Until recently, when successes were achieved in characterizing the efficacy [...] Read more.

Recent Ebola virus (EBOV) outbreaks in West Africa and the Democratic Republic of the Congo have highlighted the urgent need for approval of medical countermeasures for treatment and prevention of EBOV disease (EVD). Until recently, when successes were achieved in characterizing the efficacy of multiple experimental EVD therapeutics in humans, the only feasible way to obtain data regarding potential clinical benefits of candidate therapeutics was by conducting well-controlled animal studies. Nonclinical studies are likely to continue to be important tools for screening and development of new candidates with improved pharmacological properties. Here, we describe a natural history study to characterize the time course and order of progression of the disease manifestations of EVD in rhesus monkeys. In 12 rhesus monkeys exposed by the intramuscular route to 1000 plaque-forming units of EBOV, multiple endpoints were monitored for 28 days following exposure. The disease progressed rapidly with mortality events occurring 7–10 days after exposure. Key disease manifestations observed consistently across the infected animals included, but were not limited to, viremia, fever, systemic inflammation, coagulopathy, lymphocytolysis, renal tubular necrosis with mineralization, and hepatocellular degeneration and necrosis. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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Graphical abstract

17 pages, 1454 KiB

Open AccessCommunication

Serum LPS Associated with Hantavirus and Dengue Disease Severity in Barbados

by Kirk Osmond Douglas, Thelma Alafia Samuels and Marquita Gittens-St. Hilaire

Viruses 2019, 11(9), 838; https://doi.org/10.3390/v11090838 - 09 Sep 2019

Cited by 7 | Viewed by 3351

Abstract

Hantavirus and dengue virus (DENV) infections are caused by RNA viruses which infect immune systems’ cells including monocytes, macrophages and dendritic cells and occur year-round in Barbados. A retrospective serological study (2008–2015) was conducted on hantavirus and dengue patient sera confirmed by IgM [...] Read more.

Hantavirus and dengue virus (DENV) infections are caused by RNA viruses which infect immune systems’ cells including monocytes, macrophages and dendritic cells and occur year-round in Barbados. A retrospective serological study (2008–2015) was conducted on hantavirus and dengue patient sera confirmed by IgM and IgG ELISA, NS1 and RT-PCR using Limulus amoebocyte lysate (LAL) kinetic turbidimetric method to determine serum endotoxin levels. Hantavirus patients were categorized into two groups, namely (a) hospitalized and (b) non-hospitalized. Dengue patients were categorized into 3 groups using 2009 WHO dengue guidelines (a) severe dengue (SD), (b) hospitalized non-severe dengue (non-SD) and (c) non-hospitalized non-SD. Statistical analyses were conducted to determine the association of endotoxin levels with hantavirus disease severity based on hospitalization and dengue disease severity. Serum endotoxin levels are associated with hantavirus disease severity and hospitalization and dengue disease severity (p < 0.01). Similar studies have found an association of serum endotoxin levels with dengue disease severity but never with hantavirus infection. Co-detection of hantavirus- and DENV-specific IgM in some patients were observed with elevated serum endotoxin levels. In addition, previous studies observed hantavirus replication in the gut of patients, gastrointestinal tract as a possible entry route of infection and evidence of microbial translocation and its impact on hantavirus disease severity. A significant correlation of serum endotoxin and hantavirus disease severity and hospitalization in hantavirus infected patients is reported for the first time ever. In addition, serum endotoxin levels correlated with dengue disease severity. This study adds further support to the role of endotoxin in both hantavirus and dengue virus infection and disease severity and its role as a possible therapeutic target for viral haemorrhagic fevers (VHFs). Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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9 pages, 446 KiB

Open AccessArticle

A Methodology for Determining Which Diseases Warrant Care in a High-Level Containment Care Unit

by Theodore J. Cieslak, Jocelyn J. Herstein, Mark G. Kortepeter and Angela L. Hewlett

Viruses 2019, 11(9), 773; https://doi.org/10.3390/v11090773 - 22 Aug 2019

Cited by 5 | Viewed by 3343

Abstract

Although the concept of high-level containment care (HLCC or ‘biocontainment’), dates back to 1969, the 2014–2016 outbreak of Ebola virus disease (EVD) brought with it a renewed emphasis on the use of specialized HLCC units in the care of patients with EVD. Employment [...] Read more.

Although the concept of high-level containment care (HLCC or ‘biocontainment’), dates back to 1969, the 2014–2016 outbreak of Ebola virus disease (EVD) brought with it a renewed emphasis on the use of specialized HLCC units in the care of patients with EVD. Employment of these units in the United States and Western Europe resulted in a significant decrease in mortality compared to traditional management in field settings. Moreover, this employment appeared to significantly lessen the risk of nosocomial transmission of disease; no secondary cases occurred among healthcare workers in these units. While many now accept the wisdom of utilizing HLCC units and principles in the management of EVD (and, presumably, of other transmissible and highly hazardous viral hemorrhagic fevers, such as those caused by Marburg and Lassa viruses), no consensus exists regarding additional diseases that might warrant HLCC. We propose here a construct designed to make such determinations for existing and newly discovered diseases. The construct examines infectivity (as measured by the infectious dose needed to infect 50% of a given population (ID₅₀)), communicability (as measured by the reproductive number (R₀)), and hazard (as measured by morbidity and mortality). Diseases fulfilling all three criteria (i.e., those that are highly infectious, communicable, and highly hazardous) are considered candidates for HLCC management if they also meet a fourth criterion, namely that they lack effective and available licensed countermeasures. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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19 pages, 2825 KiB

Open AccessArticle

Characterization of Biomarker Levels in Crimean–Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome

by Miša Korva, Katarina Resman Rus, Miša Pavletič, Ana Saksida, Nataša Knap, Mateja Jelovšek, Katja Strašek Smrdel, Xhevat Jakupi, Isme Humolli, Jusuf Dedushaj, Miroslav Petrovec and Tatjana Avšič-Županc

Viruses 2019, 11(8), 686; https://doi.org/10.3390/v11080686 - 26 Jul 2019

Cited by 23 | Viewed by 3509

Abstract

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are important viral hemorrhagic fevers (VHF), especially in the Balkan region. Infections with Dobrava or Puumala orthohantavirus and Crimean-Congo hemorrhagic fever orthonairovirus can vary from a mild, nonspecific febrile illness, to a [...] Read more.

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are important viral hemorrhagic fevers (VHF), especially in the Balkan region. Infections with Dobrava or Puumala orthohantavirus and Crimean-Congo hemorrhagic fever orthonairovirus can vary from a mild, nonspecific febrile illness, to a severe disease with a fatal outcome. The pathogenesis of both diseases is poorly understood, but it has been suggested that a host’s immune mechanism might influence the pathogenesis of the diseases and survival. The aim of our study is to characterize cytokine response in patients with VHF in association with the disease progression and viral load. Forty soluble mediators of the immune response, coagulation, and endothelial dysfunction were measured in acute serum samples in 100 HFRS patients and 70 CCHF patients. HFRS and CCHF patients had significantly increased levels of IL-6, IL-12p70, IP-10, INF-γ, TNF-α, GM-CSF, MCP-3, and MIP-1b in comparison to the control group. Interestingly, HFRS patients had higher concentrations of serum MIP-1α, MIP-1β, which promote activation of macrophages and NK cells. HFRS patients had increased concentrations of IFN-γ and TNF-α, while CCHF patients had significantly higher concentrations of IFN-α and IL-8. In both, CCHF and HFRS patients’ viral load significantly correlated with IP-10. Patients with fatal outcome had significantly elevated concentrations of IL-6, IFN-α2 and MIP-1α, while GRO-α, chemokine related to activation of neutrophils and basophils, was downregulated. Our study provided a comprehensive characterization of biomarkers released in the acute stages of CCHF and HFRS. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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18 pages, 2486 KiB

Open AccessArticle

Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera

by Janusz T. Paweska, Naazneen Moolla, Nadia Storm, Veerle Msimang, Ousman Conteh, Jacqueline Weyer and Petrus Jansen van Vuren

Viruses 2019, 11(8), 678; https://doi.org/10.3390/v11080678 - 24 Jul 2019

Cited by 3 | Viewed by 3352

Abstract

Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays. Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. One I-ELISA was based [...] Read more.

Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays. Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. One I-ELISA was based on a whole EBOV antigen (WAg) and two utilized recombinant nucleocapsid (NP) and glycoproteins (GP), respectively. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). At the cut-off values selected at 95% accuracy level by the two-graph receiver operating characteristic analysis, specificity in the SA EBOV negative serum panel (n = 273) ranged from 98.17% (GP ELISA) to 99.27% (WAg ELISA). Diagnostic specificity in the SL EBOV negative panel (n = 676) was 100% by the three ELISAs. The diagnostic sensitivity in 423 RT-PCR confirmed EBOD patients was dependent on the time when the serum was collected after onset of disease. It significantly increased 2 weeks post-onset, reaching 100% sensitivity by WAg and NP and 98.1% by GP I-ELISA. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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11 pages, 1050 KiB

Open AccessArticle

Haemostatic Changes in Five Patients Infected with Ebola Virus

by Sophie J. Smither, Lyn M. O’Brien, Lin Eastaugh, Tom Woolley, Mark Lever, Tom Fletcher, Kiran Parmar, Beverley J. Hunt, Sarah Watts and Emrys Kirkman

Viruses 2019, 11(7), 647; https://doi.org/10.3390/v11070647 - 15 Jul 2019

Cited by 26 | Viewed by 3795

Abstract

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were [...] Read more.

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged. Collecting plasma without centrifugation only affected D-dimer values. Patients with Ebola virus disease had higher PT and APTT and D-dimer values than healthy humans with plasma collected in the same manner. Fibrinogen levels in patients with Ebola virus disease were normal or lower than values measured in healthy people. Clotting times and D-dimer levels were elevated during infection with Ebola virus but return to normal over time in patients that survived and therefore could be considered prognostic. Informative data can be obtained from plasma collected without centrifugation which could improve patient monitoring in hazardous environments. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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18 pages, 4458 KiB

Open AccessArticle

Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses

by Nicolas Baillet, Sophie Krieger, Alexandra Journeaux, Valérie Caro, Frédéric Tangy, Pierre-Olivier Vidalain and Sylvain Baize

Viruses 2019, 11(3), 293; https://doi.org/10.3390/v11030293 - 23 Mar 2019

Cited by 11 | Viewed by 4098

Abstract

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic [...] Read more.

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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9 pages, 2566 KiB

Open AccessArticle

Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus

by Justine Schaeffer, Stéphanie Reynard, Xavier Carnec, Natalia Pietrosemoli, Marie-Agnès Dillies and Sylvain Baize

Viruses 2019, 11(3), 287; https://doi.org/10.3390/v11030287 - 21 Mar 2019

Cited by 7 | Viewed by 3284

Abstract

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of [...] Read more.

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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20 pages, 3787 KiB

Open AccessArticle

Bovine Herpesvirus Type 4 (BoHV-4) Vector Delivering Nucleocapsid Protein of Crimean-Congo Hemorrhagic Fever Virus Induces Comparable Protective Immunity against Lethal Challenge in IFNα/β/γR−/− Mice Models

by Touraj Aligholipour Farzani, Katalin Földes, Alireza Hanifehnezhad, Burcu Yener Ilce, Seval Bilge Dagalp, Neda Amirzadeh Khiabani, Koray Ergünay, Feray Alkan, Taner Karaoglu, Hurrem Bodur and Aykut Ozkul

Viruses 2019, 11(3), 237; https://doi.org/10.3390/v11030237 - 09 Mar 2019

Cited by 27 | Viewed by 5478

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with a significant mortality rate of up to 40% in endemic areas, with evidence of geographical expansion. Due to a lack of effective therapeutics and control measures, the development of [...] Read more.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with a significant mortality rate of up to 40% in endemic areas, with evidence of geographical expansion. Due to a lack of effective therapeutics and control measures, the development of a protective CCHFV vaccine remains a crucial public health task. This paper describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4)-based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity in BALB/c and protection potential in IFNα/β/γR−/− mice models in comparison with two routinely used vaccine platforms, namely, Adenovirus type 5 and a DNA vector (pCDNA3.1 myc/His A), expressing the same antigen. All vaccine constructs successfully elicited significantly elevated cytokine levels and specific antibody responses in immunized BALB/c and IFNα/β/γR−/− mice. However, despite highly specific antibody responses in both animal models, the antibodies produced were unable to neutralize the virus in vitro. In the challenge experiment, only the BoHV4-∆TK-CCHFV-N and Ad5-N constructs produced 100% protection against lethal doses of the CCHFV Ank-2 strain in IFNα/β/γR−/− mice. The delivery platforms could not be compared due to similar protection rates in IFNα/β/γR−/− mice. However, during the challenge experiment in the T cell and passive antibody transfer assay, BoHV4-∆TK-CCHFV-N was dominant, with a protection rate of 75% compared to others. In conclusion, vector-based CCHFV N protein expression constitutes an effective approach for vaccine development and BoHV-4 emerged as a strong alternative to previously used viral vectors. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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9 pages, 1665 KiB

Open AccessArticle

Priorities, Barriers, and Facilitators towards International Guidelines for the Delivery of Supportive Clinical Care during an Ebola Outbreak: A Cross-Sectional Survey

by Marie-Claude Battista, Christine Loignon, Lynda Benhadj, Elysee Nouvet, Srinivas Murthy, Robert Fowler, Neill K. J. Adhikari, Adnan Haj-Moustafa, Alex P. Salam, Adrienne K. Chan, Sharmistha Mishra, Francois Couturier, Catherine Hudon, Peter Horby, Richard Bedell, Michael Rekart, Jan Hajek and Francois Lamontagne

Viruses 2019, 11(2), 194; https://doi.org/10.3390/v11020194 - 23 Feb 2019

Cited by 7 | Viewed by 4756

Abstract

During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus [...] Read more.

During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus Disease (EVD). We conducted a cross-sectional survey of key stakeholders involved in the response to the 2014–2016 West African EVD outbreak. Out of 57 email invitations, 44 responses were received, and 29 respondents completed the survey. The respondents listed insufficient numbers of health workers (23/29, 79%), improper tools for the documentation of clinical data (n = 22/28, 79%), insufficient material resources (n = 22/29, 76%), and unadapted personal protective equipment (n = 20/28, 71%) as the main barriers to the provision of supportive care in ETUs. Facilitators to the provision of supportive care included team camaraderie (n in agreement = 25/28, 89%), ability to speak the local language (22/28, 79%), and having treatment protocols in place (22/28, 79%). This survey highlights a consensus across various stakeholders involved in the response to the 2014–2016 EVD outbreak on a limited number of high-priority supportive care interventions for clinical practice guidelines. Identified barriers and facilitators further inform the application of guidelines. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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19 pages, 5061 KiB

Open AccessArticle

Co-Delivery Effect of CD24 on the Immunogenicity and Lethal Challenge Protection of a DNA Vector Expressing Nucleocapsid Protein of Crimean Congo Hemorrhagic Fever Virus

by Touraj Aligholipour Farzani, Alireza Hanifehnezhad, Katalin Földes, Koray Ergünay, Erkan Yilmaz, Hiba Hashim Mohamed Ali and Aykut Ozkul

Viruses 2019, 11(1), 75; https://doi.org/10.3390/v11010075 - 17 Jan 2019

Cited by 19 | Viewed by 5212

Abstract

Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection, with an eminent risk of fatal human disease. The imminent public health threat posed by the disseminated virus activity and lack of an approved therapeutic make CCHFV [...] Read more.

Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection, with an eminent risk of fatal human disease. The imminent public health threat posed by the disseminated virus activity and lack of an approved therapeutic make CCHFV an urgent target for vaccine development. We described the construction of a DNA vector expressing a nucleocapsid protein (N) of CCHFV (pV-N13), and investigated its potential to stimulate the cytokine and total/specific antibody responses in BALB/c and a challenge experiment in IFNAR^−/− mice. Because of a lack of sufficient antibody stimulation towards the N protein, we have selected cluster of differentiation 24 (CD24) protein as a potential adjuvant, which has a proliferative effect on B and T cells. Overall, our N expressing construct, when administered solely or in combination with the pCD24 vector, elicited significant cellular and humoral responses in BALB/c, despite variations in the particular cytokines and total antibodies. However, the stimulated antibodies produced as a result of the N protein expression have shown no neutralizing ability in the virus neutralization assay. Furthermore, the challenge experiments revealed the protection potential of the N expressing construct in an IFNAR ^−/− mice model. The cytokine analysis in the IFNAR^−/− mice showed an elevation in the IL-6 and TNF-alpha levels. In conclusion, we have shown that targeting the S segment of CCHFV can be considered for a practical way to develop a vaccine against this virus, because of its ability to induce an immune response, which leads to protection in the challenge assays in the interferon (IFN)-gamma defective mice models. Moreover, CD24 has a prominent immunologic effect when it co-delivers with a suitable foreign gene expressing vector. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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15 pages, 1616 KiB

Open AccessArticle

Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone

by Petrus Jansen van Vuren, Jason T. Ladner, Antoinette A. Grobbelaar, Michael R. Wiley, Sean Lovett, Mushal Allam, Arshad Ismail, Chantel le Roux, Jacqueline Weyer, Naazneen Moolla, Nadia Storm, Joe Kgaladi, Mariano Sanchez-Lockhart, Ousman Conteh, Gustavo Palacios and Janusz T. Paweska

Viruses 2019, 11(1), 71; https://doi.org/10.3390/v11010071 - 16 Jan 2019

Cited by 3 | Viewed by 5127

Abstract

We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014–2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected [...] Read more.

We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014–2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected Western Area division of SLE. The combined dataset was utilized to produce phylogenetic and phylodynamic inferences, to study sink–source dynamics and virus dispersal from highly-populated transmission hotspots. We identified four districts in SLE where EBOV was introduced and transmission occurred without onward exportation to other districts. We also identified six districts that substantially contributed to the dispersal of the virus and prolonged the EVD outbreak: five of these served as major hubs, with lots of movement in and out, and one acted primarily as a source, exporting the virus to other areas of the country. Positive correlations between case numbers, inter-district transition events, and district population sizes reaffirm that population size was a driver of EBOV transmission dynamics in SLE. The data presented here confirm the role of urban hubs in virus dispersal and of a delayed laboratory response in the expansion and perpetuation of the EVD outbreak in SLE. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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Review

Jump to: Research, Other

12 pages, 671 KiB

Open AccessReview

The Role of Reference Materials in the Research and Development of Diagnostic Tools and Treatments for Haemorrhagic Fever Viruses

by Giada Mattiuzzo, Emma M. Bentley and Mark Page

Viruses 2019, 11(9), 781; https://doi.org/10.3390/v11090781 - 24 Aug 2019

Cited by 6 | Viewed by 3118

Abstract

Following the Ebola outbreak in Western Africa in 2013–16, a global effort has taken place for preparedness for future outbreaks. As part of this response, the development of vaccines, treatments and diagnostic tools has been accelerated, especially towards pathogens listed as likely to [...] Read more.

Following the Ebola outbreak in Western Africa in 2013–16, a global effort has taken place for preparedness for future outbreaks. As part of this response, the development of vaccines, treatments and diagnostic tools has been accelerated, especially towards pathogens listed as likely to cause an epidemic and for which there are no current treatments. Several of the priority pathogens identified by the World Health Organisation are haemorrhagic fever viruses. This review provides information on the role of reference materials as an enabling tool for the development and evaluation of assays, and ultimately vaccines and treatments. The types of standards available are described, along with how they can be applied for assay harmonisation through calibration as a relative potency to a common arbitrary unitage system (WHO International Unit). This assures that assay metrology is accurate and robust. We describe reference materials that have been or are being developed for haemorrhagic fever viruses and consider the issues surrounding their production, particularly that of biosafety where the viruses require specialised containment facilities. Finally, we advocate the use of reference materials at early stages, including research and development, as this helps produce reliable assays and can smooth the path to regulatory approval. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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19 pages, 1748 KiB

Open AccessReview

Pulmonary Involvement during the Ebola Virus Disease

by Eleonora Lalle, Mirella Biava, Emanuele Nicastri, Francesca Colavita, Antonino Di Caro, Francesco Vairo, Simone Lanini, Concetta Castilletti, Martin Langer, Alimuddin Zumla, Gary Kobinger, Maria R. Capobianchi and Giuseppe Ippolito

Viruses 2019, 11(9), 780; https://doi.org/10.3390/v11090780 - 24 Aug 2019

Cited by 6 | Viewed by 4689

Abstract

Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, [...] Read more.

Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013–2016 Ebola outbreak. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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27 pages, 735 KiB

Open AccessReview

Animal Models for Crimean-Congo Hemorrhagic Fever Human Disease

by Aura R. Garrison, Darci R. Smith and Joseph W. Golden

Viruses 2019, 11(7), 590; https://doi.org/10.3390/v11070590 - 28 Jun 2019

Cited by 48 | Viewed by 5353

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important tick-borne human pathogen endemic throughout Asia, Africa and Europe. CCHFV is also an emerging virus, with recent outbreaks in Western Europe. CCHFV can infect a large number of wild and domesticated mammalian species and some [...] Read more.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important tick-borne human pathogen endemic throughout Asia, Africa and Europe. CCHFV is also an emerging virus, with recent outbreaks in Western Europe. CCHFV can infect a large number of wild and domesticated mammalian species and some avian species, however the virus does not cause severe disease in these animals, but can produce viremia. In humans, CCHFV infection can lead to a severe, life-threating disease characterized by hemodynamic instability, hepatic injury and neurological disorders, with a worldwide lethality rate of ~20–30%. The pathogenic mechanisms of CCHF are poorly understood, largely due to the dearth of animal models. However, several important animal models have been recently described, including novel murine models and a non-human primate model. In this review, we examine the current knowledge of CCHF-mediated pathogenesis and describe how animal models are helping elucidate the molecular and cellular determinants of disease. This information should serve as a reference for those interested in CCHFV animal models and their utility for evaluation of medical countermeasures (MCMs) and in the study of pathogenesis. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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7 pages, 303 KiB

Open AccessBrief Report

Clinical Evaluation of QuickNavi^TM-Ebola in the 2018 Outbreak of Ebola Virus Disease in the Democratic Republic of the Congo

by Sheila Makiala, Daniel Mukadi, Anja De Weggheleire, Shino Muramatsu, Daisuke Kato, Koichi Inano, Fumio Gondaira, Masahiro Kajihara, Reiko Yoshida, Katendi Changula, Aaron Mweene, Placide Mbala-Kingebeni, Jean-Jacques Muyembe-Tamfum, Justin Masumu, Steve Ahuka and Ayato Takada

Viruses 2019, 11(7), 589; https://doi.org/10.3390/v11070589 - 28 Jun 2019

Cited by 14 | Viewed by 3765

Abstract

The recent large outbreaks of Ebola virus disease (EVD) in West Africa and the Democratic Republic of the Congo (DRC) have highlighted the need for rapid diagnostic tests to control this disease. In this study, we clinically evaluated a previously developed immunochromatography-based kit, [...] Read more.

The recent large outbreaks of Ebola virus disease (EVD) in West Africa and the Democratic Republic of the Congo (DRC) have highlighted the need for rapid diagnostic tests to control this disease. In this study, we clinically evaluated a previously developed immunochromatography-based kit, QuickNavi^TM-Ebola. During the 2018 outbreaks in DRC, 928 blood samples from EVD-suspected cases were tested with QuickNavi^TM-Ebola and the WHO-approved GeneXpert. The sensitivity and specificity of QuickNavi^TM-Ebola, estimated by comparing it to GeneXpert-confirmed cases, were 85% (68/80) and 99.8% (846/848), respectively. These results indicate the practical reliability of QuickNavi^TM-Ebola for point-of-care diagnosis of EVD. Full article

(This article belongs to the Special Issue Medical Advances in Viral Hemorrhagic Fever Research)

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