Persistence of Zika Virus in Semen After Acute Infection

Zika Virus Clinical Trial

Official title:

Persistence of Zika Virus in Semen After Acute Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02733796
• Other study ID #: B300201628191
• Status: Completed
• Start date: February 1, 2016
• Est. completion date: September 1, 2017

Study information

• Verified date: March 2021
• Source: Institute of Tropical Medicine, Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 1, 2017
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Transmission
• Virus Diseases
• Virus Shedding
• Zika Virus
• Zika Virus Disease
• Zika Virus Infection

Locations

Country	Name	City	State
Belgium	ITM	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Tropical Medicine, Belgium

Country where clinical trial is conducted

Belgium, 

References & Publications (8)

Barzon L, Pacenti M, Franchin E, Pagni S, Martello T, Cattai M, Cusinato R, Palù 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. — View Citation

Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, Lanciotti RS, Tesh RB. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011 May;17(5):880-2. doi: 10.3201/eid1705.101939. — View Citation

Gourinat AC, O'Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis. 2015 Jan;21(1):84-6. doi: 10.3201/eid2101.140894. — View Citation

Hirayama T, Mizuno Y, Takeshita N, Kotaki A, Tajima S, Omatsu T, Sano K, Kurane I, Takasaki T. Detection of dengue virus genome in urine by real-time reverse transcriptase PCR: a laboratory diagnostic method useful after disappearance of the genome in serum. J Clin Microbiol. 2012 Jun;50(6):2047-52. doi: 10.1128/JCM.06557-11. Epub 2012 Mar 21. — View Citation

Korhonen EM, Huhtamo E, Virtala AM, Kantele A, Vapalahti O. Approach to non-invasive sampling in dengue diagnostics: exploring virus and NS1 antigen detection in saliva and urine of travelers with dengue. J Clin Virol. 2014 Nov;61(3):353-8. doi: 10.1016/j.jcv.2014.08.021. Epub 2014 Sep 1. — View Citation

Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015 Feb;21(2):359-61. doi: 10.3201/eid2102.141363. Erratum in: Emerg Infect Dis. 2015 Mar;21(3):552. — View 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. — View Citation

Poloni TR, Oliveira AS, Alfonso HL, Galvão LR, Amarilla AA, Poloni DF, Figueiredo LT, Aquino VH. Detection of dengue virus in saliva and urine by real time RT-PCR. Virol J. 2010 Jan 27;7:22. doi: 10.1186/1743-422X-7-22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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

External Links

•   Fiocruz A. Ministério da Saúde divulga boletim epidemiológico. 2015;(17):59-61
•   World Health Organization declares Public Health Emergency of International Concern