Persistence of Zika Virus in Semen After Acute Infection

Completed

• Conditions: Zika Virus; Virus Shedding; Zika Virus Disease; Transmission

• Registration Number: NCT02733796
• Lead Sponsor: Institute of Tropical Medicine, Belgium

Brief Summary

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

Objectives

1. To assess the duration of persistence of zika virus (ZIKV) in semen samples by means of RT-PCR, after acute ZIKV infection.

2. 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.

Study Timeline

• Study Start: 2016-02-01
• Study First Submitted: 2016-03-30
• Study First Submitted QC: 2016-04-05
• Study First Posted: 2016-04-12
• Primary Completion: 2017-05-01
• Study Completion: 2017-09-01
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-01
• Last Update Posted: 2021-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

ITM; 🇧🇪 Antwerp, Belgium