Rigorous #surveillance is necessary for high confidence in end-of- #outbreak #declarations for #Ebola and other infectious diseases (Philos Trans Roy Soc B., abstract)

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

Philos Trans R Soc Lond B Biol Sci. 2019 Jul 8;374(1776):20180431. doi: 10.1098/rstb.2018.0431.

Rigorous surveillance is necessary for high confidence in end-of-outbreak declarations for Ebola and other infectious diseases.

Thompson RN1,2,3, Morgan OW4, Jalava K5.

Author information: 1 Department of Zoology, University of Oxford , Oxford , UK. 2 Mathematical Institute, University of Oxford , Oxford , UK. 3 Christ Church, University of Oxford , Oxford , UK. 4 World Health Organization , Geneva , Switzerland. 5 University of Helsinki , Helsinki , Finland.

 

Abstract

The World Health Organization considers an Ebola outbreak to have ended once 42 days have passed since the last possible exposure to a confirmed case. Benefits of a quick end-of-outbreak declaration, such as reductions in trade/travel restrictions, must be balanced against the chance of flare-ups from undetected residual cases. We show how epidemiological modelling can be used to estimate the surveillance level required for decision-makers to be confident that an outbreak is over. Results from a simple model characterizing an Ebola outbreak suggest that a surveillance sensitivity (i.e. case reporting percentage) of 79% is necessary for 95% confidence that an outbreak is over after 42 days without symptomatic cases. With weaker surveillance, unrecognized transmission may still occur: if the surveillance sensitivity is only 40%, then 62 days must be waited for 95% certainty. By quantifying the certainty in end-of-outbreak declarations, public health decision-makers can plan and communicate more effectively. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This issue is linked with the earlier theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.

KEYWORDS: Ebola virus disease; World Health Organization; end-of-outbreak declarations; outbreak forecasting; surveillance

PMID: 31104606 DOI: 10.1098/rstb.2018.0431

Keywords: Ebola; Infectious Diseases.

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Longitudinal #Analysis of the #Human B Cell Response to #Ebola Virus #Infection (Cell, abstract)

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

Cell. 2019 May 10. pii: S0092-8674(19)30455-6. doi: 10.1016/j.cell.2019.04.036. [Epub ahead of print]

Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection.

Davis CW1, Jackson KJL2, McElroy AK3, Halfmann P4, Huang J1, Chennareddy C1, Piper AE5, Leung Y6, Albariño CG7, Crozier I8, Ellebedy AH9, Sidney J10, Sette A11, Yu T12, Nielsen SCA13, Goff AJ5, Spiropoulou CF7, Saphire EO14, Cavet G6, Kawaoka Y15, Mehta AK16, Glass PJ5, Boyd SD13, Ahmed R17.

Author information: 1 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. 2 Department of Pathology, Stanford University, Stanford, CA, USA; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. 3 Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA; Division of Pediatric Infectious Disease, Emory University, Atlanta, GA, USA; Division of Pediatric Infectious Disease, University of Pittsburgh, Pittsburgh, PA, USA. 4 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA. 5 Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD, USA. 6 Atreca, Redwood City, CA, USA. 7 Viral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA. 8 Integrated Research Facility at Fort Detrick, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institutes, Frederick, MD, USA. 9 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA; Division of Immunobiology, Department of Pathology and Immunology Washington University School of Medicine, St. Louis, MO, USA. 10 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. 11 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; Department of Medicine, University of California San Diego, La Jolla, CA, USA. 12 Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA. 13 Department of Pathology, Stanford University, Stanford, CA, USA. 14 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA; La Jolla Institute for Immunology, La Jolla, CA, USA. 15 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA; Division of Virology, Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 16 Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA. 17 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. Electronic address: rahmed@emory.edu.

 

Abstract

Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: B cell repertoire; Ebola; IgG subclass; antibody evolution; public clonotype

PMID: 31104840 DOI: 10.1016/j.cell.2019.04.036

Keywords: Ebola; Immunology; Immunoglobulins; Serology.

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Complete #Genome #Sequence of a New #Ebola Virus Strain Isolated during the 2017 #Likati #Outbreak in the #DRC (Microbiol Resour Announc., abstract)

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

Microbiol Resour Announc. 2019 May 16;8(20). pii: e00360-19. doi: 10.1128/MRA.00360-19.

Complete Genome Sequence of a New Ebola Virus Strain Isolated during the 2017 Likati Outbreak in the Democratic Republic of the Congo.

Wawina-Bokalanga T1, Vanmechelen B1, Martí-Carreras J1, Vergote V1, Vermeire K2, Muyembe-Tamfum JJ3, Ahuka-Mundeke S3, Maes P4.

Author information: 1 KU Leuven, Department of Microbiology, Immunology and Transplantation, Clinical and Epidemiological Virology Division, Rega Institute, Leuven, Belgium. 2 KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium. 3 Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo. 4 KU Leuven, Department of Microbiology, Immunology and Transplantation, Clinical and Epidemiological Virology Division, Rega Institute, Leuven, Belgium piet.maes@kuleuven.be.

 

Abstract

Genomic sequencing for early identification of Ebola virus remains a big challenge in low-income countries. Here, we report the complete genome sequence of an Ebola virus strain obtained during the 2017 Likati outbreak in the Democratic Republic of the Congo (DRC) by using the Oxford Nanopore Technologies (ONT) MinION sequencer.

Copyright © 2019 Wawina-Bokalanga et al.

PMID: 31097506 DOI: 10.1128/MRA.00360-19

Keywords: Ebola; DRC.

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Is the #Bombali virus #pathogenic in #humans? (Bioinformatics, abstract)

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

Bioinformatics. 2019 Apr 24. pii: btz267. doi: 10.1093/bioinformatics/btz267. [Epub ahead of print]

Is the Bombali virus pathogenic in humans?

Martell HJ1, Masterson SG1, McGreig JE1, Michaelis M1, Wass MN1.

Author information: 1 Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK.

 

Abstract

MOTIVATION:

The potential of the Bombali virus, a novel Ebolavirus, to cause disease in humans remains unknown. We have previously identified potential determinants of Ebolavirus pathogenicity in humans by analysing the amino acid positions that are differentially conserved (specificity determining positions; SDPs) between human pathogenic Ebolaviruses and the non-pathogenic Reston virus. Here, we include the many Ebolavirus genome sequences that have since become available into our analysis and investigate the amino acid sequence of the Bombali virus proteins at the SDPs that discriminate between human pathogenic and non-human pathogenic Ebolaviruses.

RESULTS:

The use of 1408 Ebolavirus genomes (196 in the original analysis) resulted in a set of 166 SDPs (reduced from 180), 146 (88%) of which were retained from the original analysis. This indicates the robustness of our approach and refines the set of SDPs that distinguish human pathogenic Ebolaviruses from Reston virus. At SDPs, Bombali virus shared the majority of amino acids with the human pathogenic Ebolaviruses (63.25%). However, for two SDPs in VP24 (M136L, R139S) that have been proposed to be critical for the lack of Reston virus human pathogenicity because they alter the VP24-karyopherin interaction, the Bombali virus amino acids match those of Reston virus. Thus, Bombali virus may not be pathogenic in humans. Supporting this, no Bombali virus-associated disease outbreaks have been reported, although Bombali virus was isolated from fruit bats cohabitating in close contact with humans, and anti-Ebolavirus antibodies that may indicate contact with Bombali virus have been detected in humans.

AVAILABILITY AND IMPLEMENTATION:

Data files are available from https://github.com/wasslab/EbolavirusSDPsBioinformatics2019.

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PMID: 31093647 DOI: 10.1093/bioinformatics/btz267

Keywords: Ebola; Ebola Bombali Virus.

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Association of #Ebola Virus #Infection With #Hearing Loss in Regions Where Ebola Virus Infection Is Endemic: A Systematic Review (JAMA Otolaryngol Head Neck Surg., abstract)

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

JAMA Otolaryngol Head Neck Surg. 2019 May 16. doi: 10.1001/jamaoto.2019.0710. [Epub ahead of print]

Association of Ebola Virus Infection With Hearing Loss in Regions Where Ebola Virus Infection Is Endemic: A Systematic Review.

Xu MJ1, Stanford-Moore G1, Czechowicz JA1.

Author information: 1 Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco.

 

Abstract

IMPORTANCE:

Many survivors of Ebola virus infection describe new-onset hearing loss after infection. The prevalence, severity, and pathophysiologic features of hearing loss in this population have not been well characterized.

OBJECTIVE:

To perform a systematic review of the current literature to characterize hearing loss in survivors of Ebola virus infection.

EVIDENCE REVIEW:

This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Searches through PubMed, Embase, and Google Scholar were performed to include publications written in English from January 1, 1965, to October 1, 2018. Relevant vocabulary terms and key terms related to Ebola and hearing loss were used. Two investigators independently screened the eligible studies, extracted data, and assessed quality and risk of bias.

FINDINGS:

Of 127 publications reviewed, 15 met the criteria for inclusion; 3 were retrospective case-control studies (level of evidence, 3), and 12 were cross-sectional studies or case reports (level of evidence, 4). Studies included 1775 survivors of Ebola virus infection (993 female [55.9%]) and 363 uninfected controls (186 female [51.2%]) from the Democratic Republic of the Congo, Uganda, Guinea, Liberia, and Sierra Leone. The duration of follow-up ranged from 0 to 29 months (median, 5 months). Hearing loss was reported in 147 survivors of Ebola virus infection (8.3%). Among studies that compared survivors with controls, the reported odds ratios for hearing loss in survivors was 7.50 (95% CI, 3.91-14.39; range, 1.4-12.1). Including all studies, the odds ratio of hearing loss in survivors vs controls in countries where Ebola virus infection is endemic was 1.84 (95% CI, 1.10-3.08).

CONCLUSIONS AND RELEVANCE:

Survivors of Ebola virus infection had higher rates of hearing loss than uninfected controls in regions where the infection is endemic. Further research with consistent objective methods and pure-tone audiometry may be needed to better characterize the hearing loss, understand its pathophysiologic features, and develop treatments.

PMID: 31095264 DOI: 10.1001/jamaoto.2019.0710

Keywords: Ebola; Hearing Loss.

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Identification of #Ebola Virus #Inhibitors Targeting GP2 using Principles of Molecular Mimicry (J Virol., abstract)

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

Identification of Ebola Virus Inhibitors Targeting GP2 using Principles of Molecular Mimicry

Courtney D. Singleton, Monica S. Humby, Hyun Ah Yi, Robert C. Rizzo, Amy Jacobs

DOI: 10.1128/JVI.00676-19

 

ABSTRACT

A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in the viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in viral entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion. Two computational structure-based virtual screens of ∼1.7M compounds were performed (DOCK program), against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing. Based on assessment of inhibitory activity, cytotoxicity, and target specificity, four promising candidates emerged with IC50 values in the 3-26 μM range. Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues which can be used to guide further inhibitor development and refinement targeting EBOV.

 

IMPORTANCE

The most recent Ebola Virus Disease outbreak from 2014 – 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide. The particularly high pathogenicity of the virus makes identification and development of promising lead compounds to serve as inhibitors of Ebola infection paramount. To limit viral load, the viral-host membrane fusion event can be targeted through the inhibition of the class I fusion glycoprotein of Ebolavirus. In the current work, several promising small molecule inhibitors that target the glycoprotein GP2 were identified through systematic application of structure-based computational and experimental drug design procedures.

Copyright © 2019 Singleton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Ebola; Antivirals.

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Participatory #Monitoring and #Evaluation of #Ebola #Response Activities in Lofa County, #Liberia: Some Lessons Learned (Int Q Community Health Educ., abstract)

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

Int Q Community Health Educ. 2019 May 12:272684X19846742. doi: 10.1177/0272684X19846742. [Epub ahead of print]

Participatory Monitoring and Evaluation of Ebola Response Activities in Lofa County, Liberia: Some Lessons Learned.

Hassaballa I1, Fawcett S2, Sepers C2, Reed FD2, Schultz J2, Munodawafa D3, Phori PM3, Chiriseri E4, Kouadio K3.

Author information: 1 Department of Psychology, The American University in Cairo, Egypt. 2 World Health Organization Collaborating Centre for Community Health and Development, University of Kansas, Lawrence, KS, USA. 3 WHO Regional Office for Africa, Brazzaville, Republic of Congo. 4 Department of Community Medicine, Midlands State University, Gweru, Zimbabwe.

 

Abstract

To address the Ebola outbreak in West Africa, the World Health Organization and the United Nations Children’s Fund led a multilevel and multisectoral intervention known as the Ebola response effort. Although surveillance systems were able to detect reduction in Ebola incidence, there was little understanding of the implemented activities within affected areas. To address this gap, this empirical case study examined (a) implementation of Ebola response activities and associated bending the curve of incidence of Ebola virus disease and (b) candidate factors associated with fuller implementation of the Ebola response effort. A mix of qualitative and quantitative methods were used to address these questions. A participatory monitoring and evaluation system was used to capture, code, characterize, and communicate nearly a hundred Ebola response activities implemented in Lofa County, a highly affected area in Liberia. The Ebola response effort was enabled by community engagement and collaboration across different sectors. Results showed fuller implementation corresponded with a marked reduction in Ebola virus disease. This report concludes with a discussion of how monitoring and evaluation can strengthen implementation of activities needed to address disease outbreaks.

KEYWORDS: Ebola; Liberia; Lofa County; participatory evaluation

PMID: 31081453 DOI: 10.1177/0272684X19846742

Keywords: Ebola; Liberia; Society.

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