Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study

被引：86

作者：

Sissoko, Daouda ^{[1
,2
]}

Duraffour, Sophie ^{[3
,4
]}

Kerber, Romy ^{[4
,5
]}

Kolie, Jacques Seraphin ^{[6
]}

Beavogui, Abdoul Habib ^{[6
]}

Camara, Alseny-Modet ^{[7
]}

Colin, Geraldine ^{[1
,8
]}

Rieger, Toni ^{[4
,5
]}

Oestereich, Lisa ^{[4
,5
]}

Palyi, Bernadett ^{[9
]}

Wurr, Stephanie ^{[4
,5
]}

Guedj, Jeremie ^{[10
,11
]}

Thi Huyen Tram Nguyen ^{[10
,11
]}

Eggo, Rosalind M. ^{[12
]}

Watson, Conall H. ^{[12
]}

Edmunds, W. John ^{[12
]}

Bore, Joseph Akoi ^{[3
,13
]}

Koundouno, Fara Raymond ^{[3
,13
]}

Cabeza-Cabrerizo, Mar ^{[3
,4
]}

Carter, Lisa L. ^{[3
,14
]}

Kafetzopoulou, Liana Eleni ^{[3
,15
]}

Kuisma, Eeva ^{[3
,16
]}

Michel, Janine ^{[3
,17
]}

Patrono, Livia Victoria ^{[3
,4
]}

Rickett, Natasha Y. ^{[3
,18
]}

Singethan, Katrin ^{[3
,19
]}

Rudolf, Martin ^{[4
,5
]}

Lander, Angelika ^{[17
]}

Pallasch, Elisa ^{[4
,5
]}

Bockholt, Sabrina ^{[4
,5
]}

Rodriguez, Estefana ^{[5
,20
]}

Di Caro, Antonino ^{[3
,21
]}

Wolfel, Roman ^{[3
,22
]}

Gabriel, Martin ^{[3
,4
]}

Gurry, Celine ^{[23
]}

Formenty, Pierre ^{[23
]}

Keita, Sakoba ^{[13
]}

Malvy, Denis ^{[1
,2
]}

Carroll, Miles W. ^{[3
,16
,24
]}

Anglaret, Xavier ^{[1
,8
]}

Guenther, Stephan ^{[3
,4
,5
]}

机构：

[1] Bordeaux Univ, INSERM, U1219, Bordeaux, France

[2] Bordeaux Univ Hosp, Bordeaux, France

[3] European Mobile Lab Consortium, Hamburg, Germany

[4] Bernhard Nocht Inst Trop Med, Bernhard Nocht Str 74, D-20359 Hamburg, Germany

[5] Partner Site Hamburg, German Ctr Infect Res DZIF, Hamburg, Germany

[6] Ctr Format & Rech Sante Rurale Maferinyah, Conakry, Guinea

[7] Donka Hosp, Dept Infect Dis, Conakry, Guinea

[8] Treichville Univ Hosp, PAC CI, ANRS Res Site, Abidjan, Cote Ivoire

[9] Hungarian Natl Biosafety Lab, Natl Ctr Epidemiol, Budapest, Hungary

[10] INSERM, IAME, UMR 1137, Paris, France

[11] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France

[12] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England

[13] Minist Hlth Guinea, Conakry, Guinea

[14] UCL, London, England

[15] Katholieke Univ Leuven, Lab Clin & Epidemiol Virol, Dept Microbiol & Immunol, Leuven, Belgium

[16] Publ Hlth England, Salisbury, Wilts, England

[17] Robert Koch Inst, Berlin, Germany

[18] Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England

[19] Tech Univ Munich, Inst Virol, Munich, Germany

[20] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[21] Natl Inst Infect Dis Lazzaro Spallanzani, Rome, Italy

[22] Bundeswehr Inst Microbiol, Munich, Germany

[23] WHO, Geneva, Switzerland

[24] Univ Southampton, South Gen Hosp, Southampton, Hants, England

来源：

LANCET GLOBAL HEALTH | 2017年 / 5卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

SEXUAL TRANSMISSION; HEMORRHAGIC-FEVER; CONGO; KIKWIT;

D O I：

10.1016/S2214-109X(16)30243-1

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Background By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. Methods In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. Findings We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0.58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. Interpretation Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.

引用

页码：E80 / E88

页数：9

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