Machine-learning #Prognostic #Models from the 2014-16 #Ebola #Outbreak: Data-harmonization Challenges, Validation Strategies, and mHealth Applications (EClinicalMedicine, abstract)

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

EClinicalMedicine. 2019 Jun 22;11:54-64. doi: 10.1016/j.eclinm.2019.06.003. eCollection 2019 May-Jun.

Machine-learning Prognostic Models from the 2014-16 Ebola Outbreak: Data-harmonization Challenges, Validation Strategies, and mHealth Applications.

Colubri A1,2,3, Hartley MA4,5, Siakor M6, Wolfman V6, Felix A2, Sesay T7, Shaffer JG8, Garry RF9, Grant DS10, Levine AC6,11, Sabeti PC1,2,3,12.

Author information: 1 Harvard University, Department of Organismic and Evolutionary Biology, Cambridge, USA. 2 Broad Institute of MIT and Harvard, Cambridge, USA. 3 Howard Hughes Medical Institute, Chevy Chase, USA. 4 University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland. 5 GOAL Global, Dublin, Ireland. 6 International Medical Corps, Los Angeles, USA. 7 Ministry of Health and Sanitation, Freetown, Sierra Leone. 8 Tulane University, School of Public Health and Tropical Medicine, New Orleans, USA. 9 Tulane University, Department of Microbiology and Immunology, New Orleans, USA. 10 Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone. 11 Brown University, Warren Alpert School of Medicine, Providence, USA. 12 Harvard School of Public Health, Boston, USA.

 

Abstract

BACKGROUND:

Ebola virus disease (EVD) plagues low-resource and difficult-to-access settings. Machine learning prognostic models and mHealth tools could improve the understanding and use of evidence-based care guidelines in such settings. However, data incompleteness and lack of interoperability limit model generalizability. This study harmonizes diverse datasets from the 2014-16 EVD epidemic and generates several prognostic models incorporated into the novel Ebola Care Guidelines app that provides informed access to recommended evidence-based guidelines.

METHODS:

Multivariate logistic regression was applied to investigate survival outcomes in 470 patients admitted to five Ebola treatment units in Liberia and Sierra Leone at various timepoints during 2014-16. We generated a parsimonious model (viral load, age, temperature, bleeding, jaundice, dyspnea, dysphagia, and time-to-presentation) and several fallback models for when these variables are unavailable. All were externally validated against two independent datasets and compared to further models including expert observational wellness assessments. Models were incorporated into an app highlighting the signs/symptoms with the largest contribution to prognosis.

FINDINGS:

The parsimonious model approached the predictive power of observational assessments by experienced clinicians (Area-Under-the-Curve, AUC = 0.70-0.79, accuracy = 0.64-0.74) and maintained its performance across subcohorts with different healthcare seeking behaviors. Age and viral load contributed > 5-fold the weighting of other features and including them in a minimal model had a similar AUC, albeit at the cost of specificity.

INTERPRETATION:

Clinically guided prognostic models can recapitulate clinical expertise and be useful when such expertise is unavailable. Incorporating these models into mHealth tools may facilitate their interpretation and provide informed access to comprehensive clinical guidelines.

FUNDING: Howard Hughes Medical Institute, US National Institutes of Health, Bill & Melinda Gates Foundation, International Medical Corps, UK Department for International Development, and GOAL Global.

KEYWORDS: Clinical intuition; Data visualization; Ebola virus disease; Machine learning; Prognostic models; Severity score; Supportive care guidelines; mHealth

PMID: 31312805 PMCID: PMC6610774 DOI: 10.1016/j.eclinm.2019.06.003

Keywords: Ebola; Machine-Learning.

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#Haemostatic Changes in Five #Patients Infected with #Ebola Virus (Viruses, abstract)

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

Viruses. 2019 Jul 15;11(7). pii: E647. doi: 10.3390/v11070647.

Haemostatic Changes in Five Patients Infected with Ebola Virus.

Smither SJ1, O’Brien LM2, Eastaugh L2, Woolley T3, Lever S2, Fletcher T4, Parmar K5, Hunt BJ5, Watts S2, Kirkman E2.

Author information: 1 Chemical Biological & Radiological Division, Dstl, Porton Down SP4 0JQ, UK. sjsmither@dstl.gov.uk. 2 Chemical Biological & Radiological Division, Dstl, Porton Down SP4 0JQ, UK. 3 Royal Centre for Defence Medicine, Birmingham Research Park, Birmingham B15 2SQ, UK. 4 Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. 5 St Thomas’ Hospital Thrombosis & Haemophilia Centre & Thrombosis and Vascular Biology Group, London SE1 7EH, UK.

 

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 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.

KEYWORDS: APTT; D-dimers; Ebola virus; PT; clotting; fibrinogen; haemostasis

PMID: 31311112 DOI: 10.3390/v11070647

Keywords: Ebola.

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#Immunogenicity, Lot #Consistency, and Extended #Safety of rVSVΔG-ZEBOV-GP [#Ebola] #Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults (J Infect Dis., abstract)

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

Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults

Scott A Halperin, Rituparna Das, Matthew T Onorato, Kenneth Liu, Jason Martin, Rebecca J Grant-Klein, Rick Nichols, Beth-Ann Coller, Frans A Helmond, Jakub K Simon, V920-012 Study Team

The Journal of Infectious Diseases, jiz241, https://doi.org/10.1093/infdis/jiz241

Published: 18 July 2019

 

Abstract

Background

This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).

Methods

Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.

Results

ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.

Conclusions

Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.

Clinical Trials RegistrationNCT02503202.

Ebola, clinical trial, immunogenicity, rVSVΔG-ZEBOV-GP, vaccine

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Ebola; Vaccines.

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#Bombali Virus in Mops condylurus #Bats, #Guinea (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 9—September 2019 / Research Letter

Bombali Virus in Mops condylurus Bats, Guinea

Lyudmila S. Karan, Marat T. Makenov, Mikhail G. Korneev, Noumany Sacko, Sanaba Boumbaly, Sergey A. Yakovlev, Kerfalla Kourouma, Roman B. Bayandin, Anastasiya V. Gladysheva, Andrey V. Shipovalov, Irina A. Yurganova, Yana E. Grigorieva, Marina V. Fedorova, Svetlana A. Scherbakova, Vladimir V. Kutyrev, Alexander P. Agafonov, Renat A. Maksyutov, German A. Shipulin, Viktor V. Maleev, Mamadou Boiro, Vasiliy G. Akimkin, and Anna Y. Popova

Author affiliations: Central Research Institute of Epidemiology, Moscow, Russia (L.S. Karan, M.T. Makenov, Y.A. Grigorieva, M.V. Fedorova, V.V. Maleev, V.G. Akimkin); Russian Research Anti-Plague Institute, Saratov, Russia (M.G. Korneev, S.A. Yakovlev, S.A. Scherbakova, V.V. Kutyrev); International Center for Research of Tropical Infections in Guinea, N’Zerekore, Guinea (N. Sacko, S. Boumbaly); Research Institute of Applied Biology of Guinea, Kindia, Guinea (N. Sacko, S. Boumbaly, K. Kourouma, M. Boiro); State Research Center of Virology and Biotechnology VECTOR, Kol’tsovo, Russia (R.B. Bayandin, A.V. Gladysheva, A.V. Shipovalov, I.A. Yurganova, A.P. Agafonov, R.A. Maksyutov); Center of Strategical Planning and Biomedical Health Risks Management, Moscow (G.A. Shipulin); Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow (A.Y. Popova)

 

Abstract

In 2018, a previously unknown Ebola virus, Bombali virus, was discovered in Sierra Leone. We describe detection of Bombali virus in Guinea. We found viral RNA in internal organs of 3 Angolan free-tailed bats (Mops condylurus) trapped in the city of N’Zerekore and in a nearby village.

Keywords: Ebola; Ebola-Bombali; Bats; Guinea.

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#Progress in Elucidating Potential #Markers and Mechanisms of Rapid #Protection Conferred by the #VSV-Vectored #Ebola Virus #Vaccine (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Progress in Elucidating Potential Markers and Mechanisms of Rapid Protection Conferred by the VSV-Vectored Ebola Virus Vaccine

Gary Wong

DOI: 10.1128/mBio.01597-19

 

ABSTRACT

Research progress over the past 20 years has yielded several experimental Ebola virus (EBOV) vaccine candidates, which were shown to be effective in nonhuman primates when given 28 days before a lethal challenge. Of these, the vesicular stomatitis virus (VSV)-vectored vaccine against EBOV (VSV-EBOV) is unique at being able to induce rapid protection, with 100% survival achieved as soon as 7 days after EBOV challenge. In a recent mBio article, Menicucci et al. carried out a transcriptome analysis of host responses in monkeys immunized with VSV-EBOV from 28 to 3 days before challenge (A. R. Menicucci, A. Jankeel, H. Feldmann, A. Marzi, and I. Messaoudi, mBio 10:e00597-19, 2019, https://doi.org/10.1128/mBio.00597-19). It was found that surviving animals had a controlled innate immune response coupled with rapid adaptive immunity, but this was not detected in nonsurviving animals. These studies highlight the important role innate immunity plays in creating an antiviral state to restrict EBOV replication and ensuring enough time for the vaccine to induce an effective adaptive immune response.

The views expressed in this article do not necessarily reflect the views of the journal or of ASM.

Keywords: Ebola; Vaccines.

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#Repurposing #Quinacrine Against #Ebola Virus Infection In vivo (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Repurposing Quinacrine Against Ebola Virus Infection In vivo

Thomas R. Lane, Jason E. Comer, Alexander N. Freiberg, Peter B. Madrid, Sean Ekins

DOI: 10.1128/AAC.01142-19

 

ABSTRACT

Quinacrine hydrochloride is a small-molecule, orally bioavailable drug that has been used clinically as an antimalarial and for many other applications. A machine learning model trained on Ebola virus (EBOV) screening data identified quinacrine as a potent (nM) in vitro inhibitor. Quinacrine (25 mg/kg) was shown in the current study to protect 70% of mice (statistically significant) from a lethal challenge with mouse-adapted EBOV (maEBOV) with once daily intraperitoneal (i.p.) dosing for 8 days.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Ebola; Quinacrine; Animal models.

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#Survivors of #Ebola virus disease develop polyfunctional #antibody responses (J Infect Dis., abstract)

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

J Infect Dis. 2019 Jul 12. pii: jiz364. doi: 10.1093/infdis/jiz364. [Epub ahead of print]

Survivors of Ebola virus disease develop polyfunctional antibody responses.

Gunn BM1, Roy V1, Karim MM1, Hartnett JN2, Suscovich TJ1, Goba A3, Momoh M3,4, Sandi JD3, Kanneh L3, Andersen KG5,6, Shaffer JG7, Schieffelin JS2, Garry RF2, Grant DS3,8, Alter G1.

Author information: 1 Ragon Institute of MGH, MIT, and Harvard, Cambridge MA, USA. 2 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans LA, USA. 3 Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone. 4 Eastern Polytechnic University, Kenema, Sierra Leone. 5 Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA. 6 Scripps Research Translational Institute, La Jolla, CA, USA. 7 Department of Biostatistics and Bioinformatics, Tulane School of Public Health and Tropical Medicine. 8 Ministry of Health and Sanitation, Freetown, Sierra Leone.

 

Abstract

BACKGROUND:

Monoclonal antibodies can mediate protection against Ebola virus (EBOV) infection through direct neutralization as well as through the recruitment of innate immune effector functions. However, the antibody functional response following survival of acute EBOV disease has not been well characterized.

METHODS:

Serum antibodies from EVD survivors from Sierra Leone were profiled to capture variation in overall subclass/isotype abundance, neutralizing activity, and innate immune effector functions.

RESULTS:

Antibodies from EVD survivors exhibit robust innate immune effector functions, mediated primarily by IgG1 and IgA1.

CONCLUSIONS:

Development of functional antibodies follows survival of acute EVD.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

KEYWORDS: Ebola virus; antibody; innate immune effector function

PMID: 31301137 DOI: 10.1093/infdis/jiz364

Keywords: Ebola; Sierra Leone; Immunology.

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