Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort study.


Journal

The Lancet. Microbe
ISSN: 2666-5247
Titre abrégé: Lancet Microbe
Pays: England
ID NLM: 101769019

Informations de publication

Date de publication:
01 2022
Historique:
received: 03 02 2021
revised: 22 05 2021
accepted: 30 06 2021
entrez: 11 5 2022
pubmed: 12 5 2022
medline: 18 5 2022
Statut: ppublish

Résumé

There is anecdotal evidence for Lassa virus persistence in body fluids. We aimed to investigate various body fluids after recovery from acute Lassa fever, describe the dynamics of Lassa virus RNA load in seminal fluid, and assess the infectivity of seminal fluid. In this prospective, longitudinal, cohort study we collected plasma, urine, saliva, lacrimal fluid, vaginal fluid, and seminal fluid from Lassa fever survivors from Irrua Specialist Teaching Hospital in Edo State, Nigeria. Inclusion criteria for participants were RT-PCR-confirmed Lassa fever diagnosis and age 18 years or older. Samples were taken at discharge from hospital (month 0) and at months 0·5, 1, 3, 6, 9, 12, 18, and 24 after discharge. The primary objective of this study was to quantitatively describe virus persistence and clearance and assess the infectivity of seminal fluid. Lassa virus RNA was detected using real-time RT-PCR. Infectivity was tested in cell culture and immunosuppressed mice. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. Between Jan 31, 2018, and Dec 11, 2019, 165 participants were enrolled in the study, of whom 159 were eligible for analysis (49 women and 110 men). Low amounts of Lassa virus RNA were detected at month 0 in plasma (49 [45%] of 110 participants), urine (37 [34%]), saliva (five [5%]), lacrimal fluid (ten [9%]), and vaginal fluid (seven [21%] of 33 female participants). Virus RNA was cleared from these body fluids by month 3. However, 35 (80%) of 44 male participants had viral RNA in seminal fluid at month 0 with a median cycle threshold of 26·5. Lassa virus RNA remained detectable up to month 12 in seminal fluid. Biostatistical modelling estimated a clearance rate of 1·19 log Lassa virus RNA is shed in various body fluids after recovery from acute disease. The persistence of infectious virus in seminal fluid implies a risk of sexual transmission of Lassa fever. German Federal Ministry of Health, German Research Foundation, Leibniz Association.

Sections du résumé

BACKGROUND
There is anecdotal evidence for Lassa virus persistence in body fluids. We aimed to investigate various body fluids after recovery from acute Lassa fever, describe the dynamics of Lassa virus RNA load in seminal fluid, and assess the infectivity of seminal fluid.
METHODS
In this prospective, longitudinal, cohort study we collected plasma, urine, saliva, lacrimal fluid, vaginal fluid, and seminal fluid from Lassa fever survivors from Irrua Specialist Teaching Hospital in Edo State, Nigeria. Inclusion criteria for participants were RT-PCR-confirmed Lassa fever diagnosis and age 18 years or older. Samples were taken at discharge from hospital (month 0) and at months 0·5, 1, 3, 6, 9, 12, 18, and 24 after discharge. The primary objective of this study was to quantitatively describe virus persistence and clearance and assess the infectivity of seminal fluid. Lassa virus RNA was detected using real-time RT-PCR. Infectivity was tested in cell culture and immunosuppressed mice. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time.
FINDINGS
Between Jan 31, 2018, and Dec 11, 2019, 165 participants were enrolled in the study, of whom 159 were eligible for analysis (49 women and 110 men). Low amounts of Lassa virus RNA were detected at month 0 in plasma (49 [45%] of 110 participants), urine (37 [34%]), saliva (five [5%]), lacrimal fluid (ten [9%]), and vaginal fluid (seven [21%] of 33 female participants). Virus RNA was cleared from these body fluids by month 3. However, 35 (80%) of 44 male participants had viral RNA in seminal fluid at month 0 with a median cycle threshold of 26·5. Lassa virus RNA remained detectable up to month 12 in seminal fluid. Biostatistical modelling estimated a clearance rate of 1·19 log
INTERPRETATION
Lassa virus RNA is shed in various body fluids after recovery from acute disease. The persistence of infectious virus in seminal fluid implies a risk of sexual transmission of Lassa fever.
FUNDING
German Federal Ministry of Health, German Research Foundation, Leibniz Association.

Identifiants

pubmed: 35544114
pii: S2666-5247(21)00178-6
doi: 10.1016/S2666-5247(21)00178-6
pii:
doi:

Substances chimiques

RNA, Viral 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e32-e40

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests SG is member of the Scientific Advisory Group to advise WHO on the implementation of the WHO R&D Blueprint for action to prevent epidemics. All other authors declare no competing interests.

Auteurs

Anke Thielebein (A)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Yemisi Ighodalo (Y)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Abubakar Taju (A)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Thomas Olokor (T)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Racheal Omiunu (R)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Rita Esumeh (R)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Paulson Ebhodaghe (P)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Anieno Ekanem (A)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Ganiyu Igenegbale (G)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Rosemary Giwa (R)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Annick Renevey (A)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Julia Hinzmann (J)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Jonas Müller (J)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Elisa Pallasch (E)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Meike Pahlmann (M)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Jeremie Guedj (J)

IAME, Université de Paris-INSERM, Paris, France.

Joy Nwatuzor (J)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Oluwasola Femi Babatunde (O)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Donatus I Adomeh (DI)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Danny Asogun (D)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Nosa Akpede (N)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Sylvanus Okogbenin (S)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

Stephan Günther (S)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany. Electronic address: guenther@bni.uni-hamburg.de.

Lisa Oestereich (L)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Sophie Duraffour (S)

Bernhard Nocht Institute for Tropical Medicine and German Center for Infection Research, Hamburg, Germany.

Ephraim Ogbaini-Emovon (E)

Irrua Specialist Teaching Hospital, Irrua, Nigeria.

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