Persistence of Zika Virus in Semen After Acute Infection

Study Overview
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Brief Summary
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This is a prospective observational laboratory evaluation of the persistence rate of zika virus (ZIKV) infection in semen by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), and assessment of ZIKV replication-competence in semen by isolation of ZIKV. Evaluation of the persistence of ZIKV and its replication-competence in semen samples will increase the understanding of the risk of sexual transmission of ZIKV infection in the post-viremic phase in non-epidemic settings.

Detailed Description
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Objectives To assess the duration of persistence of zika virus (ZIKV) in semen samples by means of RT-PCR, after acute ZIKV infection. To assess replication fitness of ZIKV in semen, by isolation of ZIKV virions in culture. Study design, population, materials and methods: Prospective cohort study of persistence of zika virus (ZIKV) in semen samples of adult male patients who attend the outpatient clinic of the Institute of Tropical Medicine in Antwerp and who have a confirmed ZIKV infection (positive RT-PCR for ZIKV in a serum or urine sample at the time of inclusion). Clinical and epidemiological data will be recorded in a standardized Case Record Form (CRF). Baseline serum, blood and urine samples will be collected as required for routine clinical evaluation of an individual case and for arbovirus antibody detection assays; sampling of serum and urine collection for RT-PCR will be scheduled weekly until 2 consecutive semen samples test negative in ZIKV RT-PCR. ZIKV isolation will be attempted from each available semen sample with a positive PCR result. The semen analyses will include: sperm count, morphology, motility, leukocyte and erythrocyte count and pH of the semen. Serum at 4 weeks will be collected for ZIKV antibody detection assay. Sample size : panel of 20 ZIKV confirmed cases Endpoints: Proportion of ZIKV positive RT-PCR on semen samples over time after confirmation of acute ZIKV infection, positivity rates of ZIKV isolation from semen samples over time after acute ZIKV infection. Expected results and relevance : Evaluation of the persistence of ZIKV and its replication-competence in semen samples will increase the understanding of the risk of sexual transmission of ZIKV infection in the post-viremic phase in non-epidemic settings. This evidence will contribute to a more rational advice on preventing sexual transmission of ZIKV infection.

Official Title
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Persistence of Zika Virus in Semen After Acute Infection

Conditions
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Zika Virus, Zika Virus Disease, Virus Shedding, Transmission

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male sex Age 18 years or older Confirmed ZIKV case, defined as: Having traveled to an affected area and developing at least 2 of the following Zika virus disease compatible symptoms within 2 weeks of travel: fever defined as T≥ 37.8°C (axillary measurement), maculopapular rash, arthralgia or non-purulent conjunctivitis. Zika virus diagnosis by:RNA detection by RT-PCR in serum or urine during the first 10 days after infection, OR Four-fold or greater change in virus-specific quantitative antibody titers in paired sera, OR Virus-specific Immunoglobulin M (IgM) antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen Exclusion Criteria: History of, or ongoing urologic malignancy or urologic surgical treatment (including vasectomy). Recent (< 2 years) history of, or ongoing urinary tract infection (including prostatitis, epididymitis, sexually transmitted diseases).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of ZIKV persistence in semen | proportion of ZIKV positive semen samples in adult male patients after acute ZIKV infection over time | weekly followup (until 2 consecutive negative PCR results)- up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| kinetics of ZIKV persistence in semen | kinetics of ZIKV in semen samples by means of RT-PCR Cycle threshold (Ct-value) results after acute ZIKV infection over time | weekly followup (until 2 consecutive negative PCR results)- up to 6 months | 
| replication fitness of ZIKV in semen | assess replication fitness of ZIKV in semen, by isolation | weekly followup (until 2 consecutive negative PCR results)- up to 6 months | 
| comparison of ZIKV sequences from semen vs. non-semen samples | comparison of ZIKV sequences of virus isolated from semen vs. non-semen samples to detect potential compartmentalization | weekly followup (until 2 consecutive negative PCR results)- up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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zika virus, semen analysis, sexual transmission