The Zika infection is a viral disease that is transmitted to humans by the same mosquito that transmits Dengue and Chikungunya fever. The Zika virus has been found in various body fluids such as urine, blood and semen, but we do not know how long it persists in these fluids. For example, parts of the virus were reported to persist in semen after six months of the onset of symptoms, but we do not know if the virus can stay longer. In this way, we want to investigate how long the Zika virus can be found in other secretions besides blood and urine.

Study Hypothesis: ZIKV can be shed in human body fluids long after the time of the acute infection. Persistence of ZIKV in different body fluids may vary due to the influence of circulating specific ZIKV IgM and IgG, as well as host and environmental factors.

Little is known about Zika virus (ZIKV) biology and its pathogenesis in humans. ZIKV has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood from a several days to one week after the onset of symptoms and has also been found to persist longer in urine and semen. Without a more granular understanding of the kinetics of ZIKV infection across biologic compartments it will be difficult to devise rational measures to prevent the transmission of the virus.

This will be an observational cohort study of men and women, aged 18 years and above, including symptomatic participants with positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine and their symptomatic or asymptomatic household/sexual contacts with positive RT-PCR in blood and/or urine. Specimens to be collected at pre-established intervals and tested for ZIKV RNA by RT-PCR are blood, semen, vaginal secretions, oral fluid (saliva and crevicular fluid), tears, sweat, urine, rectal swab, menstrual blood and breast milk (if applicable). Participants will be recruited from collaborating clinics in selected locations with high population density, high circulation of the virus, strong community network, and serviced by laboratory facilities with capacity to perform the necessary tests.

All participants will be followed up for 12 months, to assess detectability at longer time intervals, reactivation or reinfection. Analyses of antibody response, including circulating immunoglobulins M and G (IgM and IgG), will be performed in parallel to RT-PCR tests. Plaque reduction neutralization test will be performed in specimens of participants who are found to be simultaneously positive for ZIKV and dengue.

Specific analysis will be performed to determine if socio-demographic characteristics, comorbidities and co-infections influence the persistence of the virus in the body fluids.

Index Case - Enrolment Inclusion criteria

• RT-PCR test positive for ZIKV in blood and/or urine specimens
• Having given consent to provide all body fluid collection, as per protocol

Exclusion criteria RT-PCR test negative for ZIKV in blood and/or urine specimens

Household contacts enrollment (or sexual contacts if index case lives alone) Inclusion criteria

• As per index case Exclusion criteria
• As per index case

This is a prospective observational cohort study. After signing a screening consent, male and female potential study participants presenting rash compatible with ZIKV infection in collaborating clinics will be tested for the presence of ZIKV in blood and urine. The following day, after providing informed consent for enrolment, those found to be RT-PCR positive for ZIKV infection, fulfilling all inclusion criteria will be enrolled and subject of regular collection of body fluids over a period of 12 months according to a pre-established schedule. Household/sexual contacts will be screened at the reference centers where the index case was diagnosed or if preferable at their household, and recruited following the same criteria. The standard care will be provided to all participants.