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      Duration of Zika Viremia in Serum

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          Abstract

          To the Editor—Zika virus emerged in French Guiana in December 2015 shortly after its first occurrence on the American continent [1]. In this context of emergence, molecular diagnostic approach is essential to confirm first human cases and to monitor the outbreak. Nevertheless, its use must be based on a robust diagnostic algorithm built from data of Zika virus RNA persistence in body fluids with minimal bias. Here, we prospectively assessed Zika virus RNA persistence by real-time reverse transcription polymerase chain reaction in the serum of 38 infected- patients at restricted time intervals from onset of symptoms until virus clearance [2]. Detection threshold was 1.8 log10 copies/mL. No censored data and no intermittent virus detection were observed. Patients were included based on Zika virus RNA detection in their serum or urine no longer after 5 days after symptom onset. The cohort comprised 13 females and 25 males with an age of 39 ± 8.8 (mean ± standard deviation) years, recruited between December 2015 and November 2016 in French Guiana, and all provided written informed consent. This study was approved by the independent ethics committee “Comité de Protection des Personnes Sud-Méditerranée I” in Marseille, France. Time to event analyses were performed using the packages survival (v 2.41.3), flexsurv (v 1.1) and survminer (v 0.4.1) in the R statistical environment [3]. An accelerated failure-time regression model (AFT) with a log-logistic error distribution was chosen over other distributions to be fitted to the data based on the lowest Akaike information criterion. The minimum and maximum Zika virus RNA clearance time observed in our cohort were 3 and 16 days after symptoms onset, respectively. Median time from symptoms onset to Zika virus RNA clearance in serum was similar with both models: 5 days (95% confidence interval [CI] 4 days, 6 days) using the nonparametric Kaplan-Meier method and 4.8 days (95% CI 4.1 days, 5.6 days) using parametric AFT regression (Figure 1). According to the AFT regression, 95% of symptomatic patients would experience a Zika RNA clearance after 10.8 days (95% CI 9.3 days, 12.6 days) post symptoms onset. No viral load nor sex effect were observed on time to Zika RNA clearance (P = .68 and P = .45, log-rank test). Figure 1. Probabilities of Zika virus RNA clearance according to time after onset of symptoms. Kaplan-Meier estimates (A) and parametric estimates (B) of the Zika virus RNA clearance probability. A table displaying number of individuals at risk of loss of Zika virus RNA detection is provided in panel A. An accelerated failure-time regression model (AFT) with a log-logistic error distribution was used to provide parametric estimates. The medians are indicated for both analyses (A, B) and the 95th percentile is provided for the parametric analysis only (B). Light gray shading denotes 95% confidence intervals. Abbreviation: CI, confidence interval. Our results are in accordance with the median estimates assessed by Eui Jeong and colleagues analyzed only from 9 imported Zika cases in South Korea [4]. However, several other studies established a median time to Zika virus clearance after symptom onset that equal or extend 10 days in plasma or whole blood [5–7]. In these works, several biases could have contributed to overestimate the duration of Zika viremia: (i) consideration of asymptomatic patients, (ii) very low sample size, (iii) weekly interval sampling, or (iv) intermittent detection in the follow-up assessment of Zika virus RNA [5–7]. Here we provide estimates of time-dependent probabilities of loss of RNA Zika virus detection after onset of symptoms by analyzing a cohort of an unprecedent sample size. Our results can provide guidance concerning the optimum time window after symptom onset for the implementation of molecular diagnosis tests on serum.

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          Most cited references 5

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          Zika Virus Infection and Prolonged Viremia in Whole-Blood Specimens

          We tested whole-blood and plasma samples from immunocompetent patients who had had benign Zika virus infections and found that Zika virus RNA persisted in whole blood substantially longer than in plasma. This finding may have implications for diagnosis of acute symptomatic and asymptomatic infections and for testing of blood donations.
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            Kinetics of Zika Viral Load in Semen.

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              Prospective Zika virus disease cohort: systematic screening.

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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                01 October 2018
                30 March 2018
                30 March 2018
                : 67
                : 7
                : 1143-1144
                Affiliations
                [1 ]Unité de Parasitologie et Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées
                [2 ]Aix Marseille Université, IRD, AP-HM, SSA, UMR Vecteurs, Infections Tropicales et Méditerranéennes (VITROME), IHU, Méditerranée Infection
                [3 ]Military Center for Epidemiology and Public Health, Marseille, France
                [4 ]French Armed Forces Health Service in French Guiana, Cayenne, French Guiana
                [5 ]Aix Marseille Université, CNRS, INSERM, IRD, SSA, UMR Sciences Economiques et Sociales de la Santé et Traitement de l’Information Médicale (SESSTIM), IHU, Méditerranée Infection, Marseille, France
                [6 ]Laboratoire de virologie, Institut Pasteur de la Guyane, Cayenne, French Guiana
                Author notes

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

                Correspondence: S. Matheus, Laboratoire de virologie, Institut Pasteur de la Guyane, 23, Ave Pasteur, BP 6010, 97306 Cayenne Cedex, French Guiana ( smatheus@ 123456pasteur-cayenne.fr ).
                Article
                ciy261
                10.1093/cid/ciy261
                6137117
                29617955
                © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

                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, please contact journals.permissions@oup.com

                Page count
                Pages: 2
                Product
                Funding
                Funded by: Direction du Service de Santé des Armées
                Award ID: 2016RC10
                Funded by: European Union
                Award ID: 653316
                Categories
                Correspondence

                Infectious disease & Microbiology

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