First year of #PrEP implementation in #France with daily or on-demand #tenofovir disoproxil fumarate/emtricitabine (J Antimicrob Chemother., abstract)

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

First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine

M Siguier, R Mera, G Pialoux, M Ohayon, L Cotte, N Valin, J Ghosn, E Cua, C Pintado, J Chas, G Barriere, F Durand, J M Molina

Journal of Antimicrobial Chemotherapy, dkz220, https://doi.org/10.1093/jac/dkz220

Published: 20 June 2019

 

Abstract

Background

In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France.

Methods

Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients’ baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription.

Results

From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35–2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84–2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57–0.82 and 0.75, 95% CI 0.57–0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation.

Conclusions

In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Issue Section: ORIGINAL RESEARCH

Keywords: HIV/AIDS; PrEP; Antivirals.

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Emergence and #spread of #ciprofloxacin-resistant Neisseria #gonorrhoeae in #NSW, #Australia: lessons from history (J Antimicrob Chemother., abstract)

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

Emergence and spread of ciprofloxacin-resistant Neisseria gonorrhoeae in New South Wales, Australia: lessons from history

Jane K Hanrahan, Tiffany R Hogan, Cameron Buckley, Ella Trembizki, Hazel Mitchell, Colleen L Lau, David M Whiley, Monica M Lahra

Journal of Antimicrobial Chemotherapy, dkz182, https://doi.org/10.1093/jac/dkz182

Published: 06 June 2019

 

Abstract

Objectives

Our aim was to investigate the emergence and spread of ciprofloxacin resistance in clinical Neisseria gonorrhoeae isolates in New South Wales, Australia, from the first reported case in 1991 until ciprofloxacin resistance was sustained at or above the WHO threshold for treatment change of 5% (1999), to inform future strategies for controlling gonococcal antimicrobial resistance.

Methods

The index isolate and all subsequent clinical isolates of ciprofloxacin-resistant N. gonorrhoeae in New South Wales from 1991 to 1999 were genotyped using a previously described method on the Agena MassARRAY iPLEX platform. Region of acquisition data, where available, were used to determine whether cases were travel associated.

Results

In New South Wales, of the 325 ciprofloxacin-resistant N. gonorrhoeae isolates reported from 1991 to 1999, 98% (320/325) were able to be recovered and 100% (320/320) were genotyped. There were 66 different genotypes, comprising 1–99 isolates each. Notably no single clone was found to account for ciprofloxacin resistance being sustained in the population, with considerable variability in genotype prevalence observed throughout the study period. A total of 65% (209/320) of genotyped isolates had information regarding the likely place of acquisition; of these, 44% (93/209) were associated with overseas travel or sexual contact with an overseas visitor. The first ciprofloxacin-resistant N. gonorrhoeae in New South Wales was associated with travel to Thailand. Index cases of each resistant genotype were significantly more likely to have been acquired overseas (51.5%), predominantly in Asia (45%, 30/66).

Conclusions

The continued importation of multiple genotypes, rather than the expansion of a single genotype, led to ciprofloxacin-resistant N. gonorrhoeae being established in New South Wales.

Topic: ciprofloxacin – gonococcal infection – asia – australia – drug resistance, microbial – genotype – neisseria gonorrhoeae – new south wales – thailand – travel – world health organization

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ciprofloxacin; Neisseria gonorrhoeae; New South Wales; Australia.

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#Risk of #HIV #transmission through condomless sex in serodifferent gay couples with the #HIV-positive partner taking suppressive #antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study

Prof Alison J Rodger, FRCP, Valentina Cambiano, PhD, Tina Bruun, RN, Prof Pietro Vernazza, MD, Simon Collins, Olaf Degen, MD, Giulio Maria Corbelli, BSc, Vicente Estrada, MD, Prof Anna Maria Geretti, FRCPath, Apostolos Beloukas, PhD, Dorthe Raben, PhD, Pep Coll, MD, Andrea Antinori, MD, Nneka Nwokolo, MBBS, Armin Rieger, MD, Prof Jan M Prins, PhD, Anders Blaxhult, MD, Prof Rainer Weber, MD, Arne Van Eeden, MD, Prof Norbert H Brockmeyer, MD, Amanda Clarke, MD, Jorge del Romero Guerrero, MD, Prof Francois Raffi, PhD, Prof Johannes R Bogner, MD, Gilles Wandeler, MD, Prof Jan Gerstoft, MD, Prof Felix Gutiérrez, PhD, Prof Kees Brinkman, PhD, Maria Kitchen, MD, Prof Lars Ostergaard, MedScD, Agathe Leon, PhD, Matti Ristola, PhD, Heiko Jessen, MD, Prof Hans-Jürgen Stellbrink, MedScD, Prof Andrew N Phillips, PhD, Prof Jens Lundgren, PhD, for thePARTNER Study Group †

Open Access / Published: May 02, 2019 / DOI: https://doi.org/10.1016/S0140-6736(19)30418-0

 

Summary

Background

The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.

Methods

The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and envsequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods.

Findings

Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).

Interpretation

Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.

Funding

National Institute for Health Research.

Keywords: HIV/AIDS; Antivirals; STI.

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Association of #HIV #PrEP With Incidence of #STIs Among Individuals at High Risk of HIV Infection (JAMA, abstract)

[Source: The Journal of the American Medical Association, full page: (LINK). Abstract, edited.]

Original Investigation / April 9, 2019

Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection

Michael W. Traeger, MSc1; Vincent J. Cornelisse, MBBS, PhD2,3,4,5; Jason Asselin, BSc1; et al Brian Price, MBA2; Norman J. Roth, MBBS4; Jeff Willcox, MBBS6; Ban Kiem Tee, MBBS7; Christopher K. Fairley, MBBS, PhD3,5; Christina C. Chang, MBBS, PhD2,5; Jude Armishaw, BNurs2; Olga Vujovic, MBBS2; Matthew Penn, MBBS8; Pauline Cundill, BM8; George Forgan-Smith, MBBS9; John Gall, MBBS, PhD9; Claire Pickett, MBBS10; Luxi Lal, BPharm1,2; Anne Mak, BPharm2; Tim D. Spelman, MBBS, MSc1,11,12; Long Nguyen, MCom1; Dean A. Murphy, PhD13,14; Kathleen E. Ryan, PhD1,2; Carol El-Hayek, MEpi1; Michael West, BA15; Simon Ruth, MSSc16; Colin Batrouney, BA16; John T. Lockwood, BN2; Jennifer F. Hoy, MBBS2; Margaret E. Hellard, MBBS, PhD1,2,11; Mark A. Stoové, PhD1,11; Edwina J. Wright, MBBS, PhD1,2,12; for the PrEPX Study Team

Author Affiliations: 1 Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia; 2 Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia; 3 Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia; 4 Prahran Market Clinic, Melbourne, Victoria, Australia; 5 Central Clinical School, Monash University, Melbourne, Victoria, Australia; 6 Northside Clinic, Melbourne, Victoria, Australia; 7 Centre Clinic, Thorne Harbour Health, Melbourne, Victoria, Australia; 8 PRONTO! Clinic, Thorne Harbour Health, Melbourne, Victoria, Australia; 9 ERA Health, Melbourne, Victoria, Australia; 10 Ballarat Community Health Centre, Ballarat, Victoria, Australia; 11 School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 12 The Peter Doherty Institute of Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia; 13 Department of Gender and Cultural Studies, University of Sydney, Sydney, New South Wales, Australia; 14 The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia; 15 Sexual Health and Viral Hepatitis Service, Department of Health and Human Services, Government of Victoria, Melbourne, Victoria, Australia; 16 Thorne Harbour Health, Melbourne, Victoria, Australia

JAMA. 2019;321(14):1380-1390. doi:10.1001/jama.2019.2947

 

Key Points

  • Question  – Is the use of HIV preexposure prophylaxis (PrEP) associated with increased risk of sexually transmitted infections (STIs) among individuals at high risk of HIV infection?
  • Findings  – In this longitudinal study of 2981 mostly gay and bisexual men who received daily HIV preexposure prophylaxis, STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 1378 participants with preenrollment STI testing data available, receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment (adjusted incidence rate ratio, 1.12).
  • Meaning  – Findings suggest the importance of frequent testing for STIs among gay and bisexual men using PrEP.

 

Abstract

Importance  

Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP).

Objective  

To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement.

Design, Setting, and Participants  

The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016–April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018.

Exposures  

Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring.

Main Outcomes and Measures  

The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378).

Results  

Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]).

Conclusions and Relevance  

Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Keywords: HIV/AIDS; Antivirals; PrEP; STIs; Australia.

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#Persistence of #Zika Virus in Body #Fluids — Final #Report (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Persistence of Zika Virus in Body Fluids — Final Report

Gabriela Paz-Bailey, M.D., Ph.D., Eli S. Rosenberg, Ph.D., Kate Doyle, M.P.H., Jorge Munoz-Jordan, Ph.D., Gilberto A. Santiago, Ph.D., Liore Klein, M.S.P.H., Janice Perez-Padilla, M.P.H., Freddy A. Medina, Ph.D., Stephen H. Waterman, M.D., M.P.H., Laura E. Adams, D.V.M., Matthew J. Lozier, Ph.D., Jorge Bertrán-Pasarell, M.D., Carlos Garcia Gubern, M.D., Luisa I. Alvarado, M.D., and Tyler M. Sharp, Ph.D. et al.

 

Abstract

Background

To estimate the frequency and duration of detectable Zika virus (ZIKV) RNA in human body fluids, we prospectively assessed a cohort of recently infected participants in Puerto Rico.

Methods

We evaluated samples obtained from 295 participants (including 94 men who provided semen specimens) in whom ZIKV RNA was detected on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay in urine or blood at an enhanced arboviral clinical surveillance site. We collected serum, urine, saliva, semen, and vaginal secretions weekly for the first month and at 2, 4, and 6 months. All specimens were tested by means of RT-PCR, and serum was tested with the use of anti–ZIKV IgM enzyme-linked immunosorbent assay. Among the participants with ZIKV RNA in any specimen at week 4, collection continued every 2 weeks thereafter until all specimens tested negative. We used parametric Weibull regression models to estimate the time until the loss of ZIKV RNA detection in each body fluid and reported the findings in medians and 95th percentiles.

Results

The medians and 95th percentiles for the time until the loss of ZIKV RNA detection were 15 days (95% confidence interval [CI], 14 to 17) and 41 days (95% CI, 37 to 44), respectively, in serum; 11 days (95% CI, 9 to 12) and 34 days (95% CI, 30 to 38) in urine; and 42 days (95% CI, 35 to 50) and 120 days (95% CI, 100 to 139) in semen. Less than 5% of participants had detectable ZIKV RNA in saliva or vaginal secretions.

Conclusions

The prolonged time until ZIKV RNA clearance in serum in this study may have implications for the diagnosis and prevention of ZIKV infection. In 95% of the men in this study, ZIKV RNA was cleared from semen after approximately 4 months. (Funded by the Centers for Disease Control and Prevention.)

Keywords: Zika Virus; Body fluids.

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#Information #Circulation in times of #Ebola: #Twitter and the #Sexual #Transmission of #Ebola by #Survivors (PLoS Curr., abstract)

[Source: PloS Currents Outbreaks, full page: (LINK). Abstract, edited.]

Information Circulation in times of Ebola: Twitter and the Sexual Transmission of Ebola by Survivors

AUGUST 28, 2018 · RESEARCH ARTICLE

AUTHORS: Celine Morin, Ida Bost, Arnaud Mercier, Jean-Pierre Dozon, Laetitia Atlani-Duault

 

ABSTRACT

Introduction:

The 2013-2015 outbreak of Ebola was by far the largest to date, affecting Guinea, Liberia, Sierra Leone, and secondarily, Nigeria, Senegal and the United States. Such an event raises questions about the circulation of health information across social networks. This article presents an analysis of tweets concerning a specific theme: the sexual transmission of the virus by survivors, at a time when there was a great uncertainty about the duration and even the possibility of such transmission.

Methods:

This article combines quantitative and qualitative analysis. From a sample of 50,000 tweets containing the words “Ebola” in French and English, posted between March 15 and November 8, 2014, we created a graphic representation of the number of tweets over time, and identified two peaks: the first between July 27 and August 16, 2014 (633 tweets) and the second between September 28 and November 8, 2014 (2,577 tweets). This sample was divided into two parts, and every accessible publication was analyzed and coded according to the authors’ objectives, feelings expressed and/or publication type.

Results:

While the results confirm the significant role played by mainstream media in disseminating information, media did not create the debate around the sexual transmission of Ebola and Twitter does not fully reflect mainstream media contents. Social media rather work like a “filter”: in the case of Ebola, Twitter preceded and amplified the debate with focusing more than the mainstream media on the sexual transmission, as expressed in jokes, questions and criticism.

Discussion:

Online debates can of course feed on journalistic or official information, but they also show great autonomy, tinged with emotions or criticisms. Although numerous studies have shown how this can lead to rumors and disinformation, our research suggests that this relative autonomy makes it possible for Twitter users to bring into the public sphere some types of information that have not been widely addressed. Our results encourage further research to understand how this “filter” works during health crises, with the potential to help public health authorities to adjust official communications accordingly. Without a doubt, the health authorities would be well advised to put in place a special watch on the comments circulating on social media (in addition to that used by the health monitoring agencies).

FUNDING STATEMENT

This work was supported by INSERM / IMMI (Institut National de la Sante et de la Recherche Medicale, the French National Institute of Health and Medical Research / and Institut de Microbiologie et Maladies Infectieuses, the Institute of Microbiology and Infectious Diseases). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords: Ebola; STI; Society.

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#Infection of #epididymal epithelial cells and #leukocytes drives #seminal shedding of #Zika virus in a mouse model (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model

Erin M. McDonald, Nisha K. Duggal, Jana M. Ritter, Aaron C. Brault

Published: August 2, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006691 / This is an uncorrected proof.

 

Abstract

While primarily a mosquito-borne virus, Zika virus (ZIKV; genus Flavivirus in the Flaviviridaefamily) is capable of being sexually transmitted. Thirty to fifty percent of men with confirmed ZIKV infection shed ZIKV RNA in their semen, and prolonged viral RNA shedding in semen can occur for more than 6 months. The cellular reservoir of ZIKV in semen is unknown, although spermatozoa have been shown to contain ZIKV RNA and antigen. Yet, spermatozoa are not a requisite for sexual transmission, as at least one case of ZIKV sexual transmission involved a vasectomized man. To determine the cellular reservoirs of ZIKV in semen, an established animal model of sexual transmission was used. The majority of virus detected in the seminal fluid of infected mice during the peak timing of sexual transmission was from the supernatant fraction, suggesting cell-free ZIKV may be largely responsible for sexual transmission. However, some ZIKV RNA was cell-associated. In the testes and epididymides of infected mice, intracellular staining of ZIKV RNA was more pronounced in spermatogenic precursors (spermatocytes and spermatogonia) than in spermatids. Visualization of intracellular negative strand ZIKV RNA demonstrated ZIKV replication intermediates in leukocytes, immature spermatids and epididymal epithelial cells in the male urogenital tract. Epididymal epithelial cells were the principal source of negative-strand ZIKV RNA during the peak timing of sexual transmission potential, indicating these cells may be the predominant source of infectious cell-free ZIKV in seminal fluid. These data promote a more complete understanding of sexual transmission of ZIKV and will inform further model development for future studies on persistent ZIKV RNA shedding.

 

Author summary

While Zika virus (ZIKV) is primarily a mosquito-borne virus, there are now confirmed sexual transmission cases of ZIKV from infected males to their partners. Using a previously established mouse model of sexual transmission, ZIKV was herein demonstrated to infect the testes and epididymides concurrently, suggesting that testicular infection is not required to seed infection of the epididymides. Also, replication of ZIKV was visualized by staining for ZIKV negative-strand RNA. ZIKV replication in leukocytes, immature spermatids and epididymal epithelial cells correlated with the peak of sexual transmission potential. Spermatozoa were rarely observed to stain positive for ZIKV replicative RNA intermediates, demonstrating spermatozoa are likely not a major source of infectious virus in semen. In addition, a greater fraction of the infectious virus in seminal fluids was cell-free versus cell-associated, suggesting that cell-free virus is responsible for sexual transmission. Taken together, these data provide strong evidence for epididymal epithelial cells and leukocytes, and not spermatozoa, as the major sources of infectious ZIKV in semen.

___

Citation: McDonald EM, Duggal NK, Ritter JM, Brault AC (2018) Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model. PLoS Negl Trop Dis 12(8): e0006691. https://doi.org/10.1371/journal.pntd.0006691

Editor: Pei-Yong Shi, University of Texas Medical Branch at Galveston, UNITED STATES

Received: May 25, 2018; Accepted: July 15, 2018; Published: August 2, 2018

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This research was made possible through support provided by the Office of Infectious Disease, Bureau for Global Health, U.S. Agency for International Development, under the terms of an Interagency Agreement with CDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus; STI; Animal Models.

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