Clinical trial NCT02733796: Persistence of Zika Virus in Semen After Acute Infection
Official title: Persistence of Zika Virus in Semen After Acute Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Zika Virus
Zika Virus Disease
Virus Shedding
Transmission
Keywords: zika virus
semen analysis
sexual transmission
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
First posted: 2016-04-12
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: men of 18 years or older, with confirmed ZIKV infection, residing in areas without epidemiologically important arthropod-borne ZIKV transmission

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Incidence rate of ZIKV persistence in semen
timeFrame: weekly followup (until 2 consecutive negative PCR results)- up to 6 months
Secondary outcomes:
measure: kinetics of ZIKV persistence in semen
timeFrame: weekly followup (until 2 consecutive negative PCR results)- up to 6 months
measure: replication fitness of ZIKV in semen
timeFrame: weekly followup (until 2 consecutive negative PCR results)- up to 6 months
measure: comparison of ZIKV sequences from semen vs. non-semen samples
timeFrame: weekly followup (until 2 consecutive negative PCR results)- up to 6 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: ITM
Study officials:
affiliation: Institute of Tropical Medicine, Antwerp, Belgium
name: Emmanuel Bottieau, MD PhD
role: STUDY_CHAIR
References:
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citation: Barzon L, Pacenti M, Franchin E, Pagni S, Martello T, Cattai M, Cusinato R, Palu G. Excretion of West Nile virus in urine during acute infection. J Infect Dis. 2013 Oct 1;208(7):1086-92. doi: 10.1093/infdis/jit290. Epub 2013 Jul 2.
citation: Oster AM, Brooks JT, Stryker JE, Kachur RE, Mead P, Pesik NT, Petersen LR. Interim Guidelines for Prevention of Sexual Transmission of Zika Virus - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):120-1. doi: 10.15585/mmwr.mm6505e1.