In vitro characterization and in vivo effectiveness of #Ebola virus specific #equine #polyclonal F(ab’)2 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

In vitro characterization and in vivo effectiveness of Ebola virus specific equine polyclonal F(ab’)2

Trina Racine, Mélanie Denizot, Delphine Pannetier, Ludovic Nguyen, Anaïs Pasquier, Hervé Raoul, Jean-François Saluzzo, Gary Kobinger, Francisco Veas, Cécile H Herbreteau

The Journal of Infectious Diseases, jiz068, https://doi.org/10.1093/infdis/jiz068

Published: 14 February 2019

 

Abstract

There is no vaccine or approved therapy against lethal Ebola virus (EBOV). We investigated a proven technology platform to produce polyclonal IgG fragments, F(ab’)2, against EBOV. Horses immunized with virus-like-particles (VLPs) harboring surface glycoprotein trimers of EBOV-Zaire/Makona produced anti-Ebola IgG polyclonal antibodies with high neutralization activity. Highly-purified equine anti-Ebola F(ab’)2 showed strong cross-neutralization of two Zaire EBOV strains (Gabon 2001 and Makona) and in vivothree or five daily F(ab’)2 intraperitoneal injections provided 100% protection to BALB/c mice against lethal EBOV challenge. Rapid preparation of purified equine anti-Ebola F(ab’)2 offers a potentially efficient therapeutic approach against EBOV disease in humans.

Ebola, immunoglobulins, equine, F(ab’)2 fragments

Issue Section: Brief Report

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Keywords: Ebola; Ebola Makona; Immunoglobulins.

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#Epidemiological characteristics, #clinical manifestations, and #treatment outcome of 139 #paediatric #Ebola patients treated at a #SierraLeone #ETC (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2019 Jan 24;19(1):81. doi: 10.1186/s12879-019-3727-7.

Epidemiological characteristics, clinical manifestations, and treatment outcome of 139 paediatric Ebola patients treated at a Sierra Leone Ebola treatment center.

Kangbai JB1,2, Heumann C3,4, Hoelscher M3,5, Sahr F6,7, Froeschl G3,5.

Author information: 1 Center for International Health, University of Munich (LMU), Munich, Germany. Jia.Kangbai@lrz.uni-muenchen.de. 2 Department of Environmental Health Sciences, Njala University, Bo, Sierra Leone. Jia.Kangbai@lrz.uni-muenchen.de. 3 Center for International Health, University of Munich (LMU), Munich, Germany. 4 Department of Statistics, University of Munich (LMU), Munich, Germany. 5 Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany. 6 Department of Microbiology, College of Medicine and Allied Health Sciences, University of Sierra Leone, Bo, Sierra Leone. 7 34 Military Hospital, Wilberforce, Freetown, Sierra Leone.

 

Abstract

BACKGROUND:

The West Africa Ebola Virus Disease (EVD) outbreak in 2014-2016 was declared by the World Health Organization (WHO) a public health emergency of international concern. Most of the previous studies done in Sierra Leone relating to the clinical and epidemiological features of EVD during the 2014-2016 West African outbreak focused on adult EVD patients. There have been conflicting reports about the effects of EVD on children during previous outbreaks.

METHODS:

This is an observational retrospective analysis of medical data of all laboratory confirmed paediatric EVD patients below 15 years of age who were admitted at the 34 Military Hospital Ebola Treatment Center (ETC) in Wilberforce, Sierra Leone between June 2014 to April 2015. We analyzed the sociodemographic and clinical characteristics of paediatric EVD cases contained in case report forms that were collected by Ebola surveillance officers and clinicians at the 34 Military Hospital ETC. Both univariate and multivariate logistic regression models were used to determine the sociodemographic and clinical characteristics of paediatric EVD patients that were associated with EVD facility-based mortality.

RESULTS:

The majority of the paediatric EVD cases in this study were female (56.1%), pupils (51.1%), and 43.2% belonged to the age group between 10 years and below 15 years. The median age of the paediatric EVD cases was 9 years (interquartile range = 4 to 11 years). Adjusting for other covariates in the model, male paediatric EVD patient (AOR = 13.4, 95% CI = [2.07-156-18], p <  0.05), EVD patient with abdominal pain (AOR = 11.0, 95% CI = [1.30-161.81], p <  0.05), vomiting (AOR = 35.7, 95% CI = [3.43-833.73], p <  0.05), signs of conjunctivitis (AOR = 17.4, 95% CI = [1.53-342.21], p <  0.05) and difficulty in breathing (AOR = 23.3, 95% CI = [1.92-713.01], p <  0.05) at the time of admission had increased odds of dying during EVD treatment.

CONCLUSIONS:

We recommend the adoption of case definitions currently in vigour to cater for specific characteristics of paediatric patients. Subgroups that can be identified by applying the model developed in this study may require special attention and intensified care.

KEYWORDS: Ebola; Ebola treatment center; Paediatric; Sierra Leone; Treatment outcome

PMID: 30678649 DOI: 10.1186/s12879-019-3727-7

Keywords: Ebola; Ebola-Makona; Sierra Leone.

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#Phylodynamic Analysis of #Ebola Virus Disease #Transmission in #SierraLeone (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Jan 16;11(1). pii: E71. doi: 10.3390/v11010071.

Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone.

Jansen van Vuren P1, Ladner JT2,3, Grobbelaar AA4, Wiley MR5,6, Lovett S7, Allam M8, Ismail A9, le Roux C10, Weyer J11, Moolla N12, Storm N13, Kgaladi J14, Sanchez-Lockhart M15, Conteh O16, Palacios G17, Paweska JT18,19.

Author information: 1 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. petrusv@nicd.ac.za. 2 Center for Genome Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. jtladner@gmail.com. 3 The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86001, USA. jtladner@gmail.com. 4 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. antoinetteg@nicd.ac.za. 5 Center for Genome Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. michael.r.wiley19.ctr@mail.mil. 6 Department of Environmental, Agricultural & Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA. michael.r.wiley19.ctr@mail.mil. 7 Center for Genome Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. Lovett05@gmail.com. 8 Sequencing Core Facility, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. mushala@nicd.ac.za. 9 Sequencing Core Facility, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. arshadi@nicd.ac.za. 10 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. chantell@nicd.ac.za. 11 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. jacquelinew@nicd.ac.za. 12 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. naazneenm@nicd.ac.za. 13 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. nadias@nicd.ac.za. 14 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. joek@nicd.ac.za. 15 Center for Genome Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. mariano.sanchez-lockhart.ctr@mail.mil. 16 Ministry of Health and Sanitation, Freetown 47235, Sierra Leone. osconteh@gmail.com. 17 Center for Genome Sciences, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, USA. gustavo.f.palacios.ctr@mail.mil. 18 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa. januszp@nicd.ac.za. 19 Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa. januszp@nicd.ac.za.

 

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 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.

KEYWORDS: Ebola virus; Ebola virus disease; Filoviridae; Sierra Leone; West Africa; filovirus; phylodynamics

PMID: 30654482 DOI: 10.3390/v11010071

Keywords: Ebola; Ebola-Makona; Sierra Leone.

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#Transplacental transmission: A rare case of #Ebola virus #transmission (Infect Dis Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Dis Rep. 2018 Dec 5;10(3):7725. doi: 10.4081/idr.2018.7725. eCollection 2018 Nov 6.

Transplacental transmission: A rare case of Ebola virus transmission.

Okoror L1, Kamara A2, Kargbo B2, Bangura J2, Lebby M2.

Author information: 1 World Health Organization and Federal University, Oye-Ekiti, Nigeria. 2 Ministry of Health and Sanitation, Freetown, Sierra Leone.

 

Abstract

During the mid-transmission period of the Ebola virus disease (EVD) outbreak in Sierra Leone, a 19-year-old pregnant woman, who was a petty trader in a health facility in Freetown, noticing no fetal movement for the past 3 days, reported to a health facility. Medical history and laboratory testing showed no abnormalities except that she was positive for sickle cell. She was not known to any surveillance team of having any epidemiological link to EVD case. She was induced with oral medications as well as IV infusion. EVD test showed that the fetus was positive to EVD with a high threshold value of 21, while the woman was negative for EVD with a threshold value of 42. The woman was positive to EVD IgG but negative to EVD IgM by ELISA technique. This is a rare EVD case in the period of medium transmission. We conclude that the woman may have come into contact with a low dose of virus not enough to cause a full blown EVD and that her immune system was able to stop the virus from further replication.

KEYWORDS: EVD; IgG; IgM; PCR; fetus; still birth

PMID: 30631407 PMCID: PMC6297901 DOI: 10.4081/idr.2018.7725

Keywords: Ebola; Pregnancy; Sierra Leone.

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Surviving #Ebola: A historical cohort study of Ebola #mortality and #survival in #SierraLeone 2014-2015 (PLoS One, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

PLoS One. 2018 Dec 27;13(12):e0209655. doi: 10.1371/journal.pone.0209655. eCollection 2018.

Surviving Ebola: A historical cohort study of Ebola mortality and survival in Sierra Leone 2014-2015.

Wing K1,2, Oza S1,2, Houlihan C3, Glynn JR2, Irvine S1, Warrell CE1, Simpson AJH4, Boufkhed S1,2, Sesay A1, Vandi L1, Sebba SC1, Shetty P5, Cummings R5, Checchi F1,2, McGowan CR1,2,5.

Author information: 1 Save the Children International, Kerry Town, Sierra Leone. 2 London School of Hygiene & Tropical Medicine, London, United Kingdom. 3 Division of Infection and Immunity, University College London, London, United Kingdom. 4 Rare and Imported Pathogens Laboratory, Public Health England, Porton, Wilts, United Kingdom. 5 Humanitarian Public Health Technical Unit, Save the Children, London, United Kingdom.

 

Abstract

BACKGROUND:

While a number of predictors for Ebola mortality have been identified, less is known about post-viral symptoms. The identification of acute-illness predictors for post-viral symptoms could allow the selection of patients for more active follow up in the future, and those in whom early interventions may be beneficial in the long term. Studying predictors of both mortality and post-viral symptoms within a single cohort of patients could also further our understanding of the pathophysiology of survivor sequelae.

METHODS/PRINCIPAL FINDINGS:

We performed a historical cohort study using data collected as part of routine clinical care from an Ebola Treatment Centre (ETC) in Kerry Town, Sierra Leone, in order to identify predictors of mortality and of post-viral symptoms. Variables included as potential predictors were sex, age, date of admission, first recorded viral load at the ETC and symptoms (recorded upon presentation at the ETC). Multivariable logistic regression was used to identify predictors. Of 263 Ebola-confirmed patients admitted between November 2014 and March 2015, 151 (57%) survived to ETC discharge. Viral load was the strongest predictor of mortality (adjusted OR comparing high with low viral load: 84.97, 95% CI 30.87-345.94). We did not find evidence that a high viral load predicted post-viral symptoms (ocular: 1.17, 95% CI 0.35-3.97; musculoskeletal: 1.07, 95% CI 0.28-4.08). Ocular post-viral symptoms were more common in females (2.31, 95% CI 0.98-5.43) and in those who had experienced hiccups during the acute phase (4.73, 95% CI 0.90-24.73).

CONCLUSIONS/SIGNIFICANCE:

These findings may add epidemiological support to the hypothesis that post-viral symptoms have an immune-mediated aspect and may not only be a consequence of high viral load and disease severity.

PMID: 30589913 DOI: 10.1371/journal.pone.0209655

Keywords: Ebola; Ebola-Makona; Sierra Leone.

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Comparative Transcriptomics in #Ebola #Makona-Infected #Ferrets, Nonhuman #Primates, and #Humans (J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Dis. 2018 Nov 22;218(suppl_5):S486-S495. doi: 10.1093/infdis/jiy455.

Comparative Transcriptomics in Ebola Makona-Infected Ferrets, Nonhuman Primates, and Humans.

Cross RW1,2, Speranza E3, Borisevich V1,2, Widen SG4, Wood TG4, Shim RS5, Adams RD5, Gerhardt DM5, Bennett RS5, Honko AN5, Johnson JC5, Hensley LE5, Geisbert TW1,2, Connor JH4,3.

Author information: 1 Galveston National Laboratory, University of Texas Medical Branch, Galveston. 2 Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston. 3 Department of Microbiology, Bioinformatics Program, National Emerging Infectious Disease Laboratories, Boston University, Massachusetts. 4 Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston. 5 Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland.

 

Abstract

The domestic ferret is a uniformly lethal model of infection for 3 species of Ebolavirus known to be pathogenic in humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and nonhuman primates infected with lethal doses of the Makona variant of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and nonhuman primates, and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.

PMID: 30476250 DOI: 10.1093/infdis/jiy455

Keywords: Ebola; Ebola-Makona; Animal models.

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Naturally-occurring single #mutations in #Ebola observably impact #infectivity (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Naturally-occurring single mutations in Ebola observably impact infectivity

Gary Wong, Shihua He, Anders Leung, Wenguang Cao, Yuhai Bi, Zirui Zhang, Wenjun Zhu, Liang Wang, Yuhui Zhao, Keding Cheng, Di Liu, Wenjun Liu, Darwyn Kobasa, George F. Gao,Xiangguo Qiu

DOI: 10.1128/JVI.01098-18

 

ABSTRACT

Sequencing of Ebola virus (EBOV) genomes during the 2014-16 epidemic identified several naturally-occurring, dominant mutations potentially impacting virulence or tropism. Here, we characterized EBOV variants carrying one of the following substitutions: A82V in the glycoprotein (GP), R111C in the nucleoprotein (NP), or D759G in the RNA-dependent RNA-polymerase (L). Compared with wild-type EBOV/C07 (WT), NP and L mutants conferred a replication advantage in monkey VeroE6, human A549 and insectivorous bat Tb1.Lu cells, while L displayed a disadvantage in human Huh7 cells. GP mutant replication was significantly delayed in Tb1.Lu and similar to WT in other cells. The L mutant was less virulent, as evidenced by increased survival in mice and a significantly delayed time to death in ferrets, but increased lengths of EBOV shedding may have contributed to the prolonged epidemic. Our results show that single substitutions can have observable impacts on EBOV pathogenicity and provide a framework to study other mutations.

 

IMPORTANCE

During the Ebola virus (EBOV) disease outbreak in West Africa in 2014-16, it was discovered that several mutations in the virus emerged and became prevalent in the human population. This suggests that these mutations may play a role impacting viral fitness. We investigated three of these previously identified mutations (in the glycoprotein (GP), nucleoprotein (NP) or RNA-dependent RNA polymerase (L)) in cell culture as well as in mice and ferrets by generating recombinant viruses (based on an early West African EBOV strain) carrying one of these mutations. The NP and L mutations appear to decrease virulence, whereas GP slightly increases virulence but mainly impacts viral tropism. Our results show that these single mutations can impact EBOV virulence in animals and have implications for the rational design of efficacious antiviral therapies against these infections.

© Crown copyright 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Ebola; Ebola-Makona.

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