Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days

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Abstract

We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.

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Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Preliminary Report.

Gibrilla Deen, Nathalie Broutet, Wenbo Xu … (2017)

Background Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD), but little information is available about its prevalence or the duration of its persistence. We report the initial findings of a pilot study involving survivors of EVD in Sierra Leone. Methods We enrolled a convenience sample of 100 male survivors of EVD in Sierra Leone, at different times after their recovery from EVD, and recorded self-reported information about sociodemographic characteristics, the EVD episode, and health status. Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target-gene sequences of NP and VP40. Results A total of 93 participants provided an initial semen specimen for analysis, of whom 46 (49%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 9 men who had a specimen obtained 2 to 3 months after the onset of EVD, in the semen of 26 of 40 (65%) who had a specimen obtained 4 to 6 months after onset, and in the semen of 11 of 43 (26%) who had a specimen obtained 7 to 9 months after onset; the results for 1 participant who had a specimen obtained at 10 months were indeterminate. The median cycle-threshold values (for which higher values indicate lower RNA levels) were 32.0 with the NP gene target and 31.1 with the VP40 gene target for specimens obtained at 2 to 3 months, 34.5 and 32.3, respectively, for specimens obtained at 4 to 6 months, and 37.0 and 35.6, respectively, for specimens obtained at 7 to 9 months. Conclusions These data showed the persistence of Ebola virus RNA in semen and declining persistence with increasing months since the onset of EVD. We do not yet have data on the extent to which positivity on RT-PCR is associated with virus infectivity. Although cases of suspected sexual transmission of Ebola have been reported, they are rare; hence the risk of sexual transmission of the Ebola virus is being investigated. (Funded by the World Health Organization and others.).

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Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa

Miles W. Carroll, David A Matthews, Julian A. Hiscox … (2015)

Analysis of 179 new Ebola virus sequences from patient samples collected in Guinea between March 2014 and January 2015 shows how different lineages evolved and spread in West Africa. Supplementary information The online version of this article (doi:10.1038/nature14594) contains supplementary material, which is available to authorized users. Miles Carroll and colleagues report describe the genetic evolution of Ebola virus circulating in West Africa, based on 179 new virus sequences from patient samples collected in Guinea between March 2014 and January 2015. Their analysis shows how different lineages evolved and spread in West Africa between Sierra Leone, Guinea and Liberia. Supplementary information The online version of this article (doi:10.1038/nature14594) contains supplementary material, which is available to authorized users. West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded 1 , 2 , 3 . Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2 ). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak. Supplementary information The online version of this article (doi:10.1038/nature14594) contains supplementary material, which is available to authorized users.

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Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995.

L. L. Rodriguez, A. de Roo, Y Guimard … (1999)

Ebola virus persistence was examined in body fluids from 12 convalescent patients by virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) during the 1995 Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo. Virus RNA could be detected for up to 33 days in vaginal, rectal, and conjunctival swabs of 1 patient and up to 101 days in the seminal fluid of 4 patients. Infectious virus was detected in 1 seminal fluid sample obtained 82 days after disease onset. Sequence analysis of an RT-PCR fragment of the most variable region of the glycoprotein gene amplified from 9 patients revealed no nucleotide changes. The patient samples were selected so that they would include some from a suspected line of transmission with at least three human-to-human passages, some from 5 survivors and 4 deceased patients, and 2 from patients who provided multiple samples through convalescence. There was no evidence of different virus variants cocirculating during the outbreak or of genetic variation accumulating during human-to-human passage or during prolonged persistence in individual patients.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Infect Dis

Journal ID (iso-abbrev): Clin. Infect. Dis

Journal ID (publisher-id): cid

Journal ID (hwp): cid

Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

Publisher: Oxford University Press

ISSN (Print): 1058-4838

ISSN (Electronic): 1537-6591

Publication date (Print): 15 November 2016

Publication date (Electronic): 01 September 2016

Publication date PMC-release: 01 September 2016

Volume: 63

Issue: 10

Pages: 1353-1356

Affiliations

[1 ]World Health Organization , Conakry, Guinea

[2 ]INSERM U1219, Bordeaux University

[3 ]Bordeaux University Hospital , France

[4 ]Institute of Microbiology and Infection, University of Birmingham , United Kingdom

[5 ]Laboratoire des Fièvres Hémorragiques en Guinée, Hôpital Donka et N'Zérékoré

[6 ]Centers for Disease Control and Prevention (CDC) Guinea Response Team , Conakry

[7 ]Center for Global Health, CDC , Atlanta, Georgia

[8 ]European Mobile Laboratory Consortium

[9 ]Bernhard Nocht Institute for Tropical Medicine , Hamburg, Germany

[10 ]Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital , United Kingdom

[11 ]Department of Public Health, University of Makeni , Sierra Leone

[12 ]Wellcome Genome Campus, Hinxton , Cambridge, United Kingdom

[13 ]Department of Biology, University of Rome II “Tor Vergata ,” Italy

[14 ]National Center for Emerging and Zoonotic Infectious Diseases , CDC, Atlanta, Georgia

[15 ]Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée , Guinea

[16 ]Programme ANRS Coopération Côte d'Ivoire, Agence Nationale de Recherche sur le Sida Research Site, Treichville University Hospital , Abidjan, Côte d'Ivoire

[17 ]Public Health England, Porton Down , Salisbury

[18 ]University of Southampton, South General Hospital , United Kingdom

[19 ]World Health Organization , Geneva, Switzerland

[20 ]Ministry of Health , Conakry, Guinea

[21 ]Institute for Evolutionary Biology, Centre for Infection, Immunity and Evolution, Ashworth Laboratories, University of Edinburgh , United Kingdom

Author notes

[a]

B. D. and D. S. contributed equally to this work.

Correspondence: S. Duraffour, Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Straße, 74, Hamburg 20359, Germany ( sophieduraffour@ 123456yahoo.fr ).

Article

Publisher ID: ciw601

DOI: 10.1093/cid/ciw601

PMC ID: 5091350

PubMed ID: 27585800

SO-VID: df6d0687-61a6-4523-acbe-befc581efc43

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@ 123456oup.com .

History

Date received : 5 July 2016

Date accepted : 17 August 2016

Funding

Funded by: European Union's Horizon;

Award ID: 666100

Award ID: 666092

Award ID: IFS/2011/272-372

Funded by: Directorate-General for International Cooperation and Development;

Award ID: C15-101

Funded by: French Institute of Health and Medical Research (INSERM);

Funded by: Wellcome Trust;

Award ID: 097997/Z/11/A

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Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days

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Most cited references 4

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Preliminary Report.

Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa

Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995.

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