Recipient Epidemiology and Donor Evaluation Study III (REDS III) U.S. Natural History Cohort of Zika Virus RNA Positive Blood Donors (U.S. Zika)

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Accession Number

Study Type
Epidemiology Study

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period

NHLBI Division

Dataset(s) Last Updated
May 4, 2020

Clinical Trial URLs

Primary Publication URLs


Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No

Additional Information

This page is for REDS III-US Zika data. Biospecimens may separately be available from the study group. For more information, visit the REDS III-US Zika non-BioLINCC resource page.


This REDS-III US Zika Natural History Study sought to investigate the dynamics of viral and serological markers and clinical symptomatology following acute Zika virus infection in nucleic acid test (NAT) -positive blood donors, and collect comprehensive data on viral persistence in blood compartments and body fluids in dengue virus (DENV)-exposed and -naïve donors to estimate time from infection to earliest detection of Zika; time to loss of detectable virus from plasma, red cells and other compartments; and time to emergence and loss of immune response to infection.


Zika virus (ZIKV) is a mosquito-borne arbovirus that can also be transmitted congenitally and through transfusion and sexual contact. It was first identified in the Zika forest in Uganda in the 1950’s. More recently, it spread to Malaysia and Indonesia, then to Micronesia, French Polynesia and, in 2014 to Brazil. Although asymptomatic or mildly symptomatic in most cases, ZIKV can cause Guillain-Barré syndrome and infection during pregnancy has been associated with intrauterine fetal death and congenital Zika syndrome. The goal of this study was to characterize viral persistence and immune responses to Zika infection following acute infection. This information is needed to inform blood donor and diagnostic testing policies and understand the natural history of ZIKV infection.


Fifty-three ZIKV-infected blood donors were enrolled in the study. Participants were identified from asymptomatic donors at participating blood centers (Banco de Sangre de Servicios Mutuos, OneBlood, Vitalant, New York Blood Center or American Red Cross) from April through December 2016, coinciding with a large ZIKV virus epidemic in Puerto Rico and small autochthonous outbreak in South Florida. Blood donor index donation plasma samples were screened using either the RMS cobas® Zika or Grifols Procleix Zika Virus NAT assays. ZIKV infection in NAT-reactive donors was confirmed by repeat-reactivity on the screening NAT assay, reactivity on a confirmatory RT-PCR assay on index plasma, or ZIKV IgM seroconversion in index or follow-up serum samples.


The study used donor NAT screening to identify and enroll asymptomatic ZIKV infected blood donors into a one-year follow-up study. The design enabled identification of donors early in acute infection (i.e., before or shortly after development of ZIKV-specific immune responses), representing a highly informative population for characterization of laboratory parameters and incidence of clinical findings.

The follow-up visits were scheduled for weeks 1, 3, 6 and months 3, 6, 9, 12 following the index NAT-reactive donation. Blood and body fluid samples and detailed symptom data were collected at these visits. All sample types were tested for ZIKV RNA by quantitative RT-PCR (qRT-PCR); follow-up plasma, whole blood (WB) and urine were also tested by replicate qualitative TMA NAT testing. Plasma was tested for flavivirus-specific IgM and IgG. Twenty-four participants were recruited before a detectable immune response (i.e. they were IgM-negative), 26 were positive for zika IgM, 2 had equivocal tests for IgM and 1 had an inconclusive test. Subjects were also tested for dengue IgG at baseline index donation; 38 were positive and 15 were negative.


Determinations of viral marker persistence are enhanced by follow-up of pre- and asymptomatic RNA+/Ab- blood donors. The study found higher rates of post-donation symptomatic infection than in most previous reports. RBC-associated ZIKV RNA persists for several months following clearance from plasma and body fluids, and replicate highly sensitive NAT testing extends RNA detection in all compartments. WB testing can extend detection of acute infection for diagnostics and monitoring of pregnant women, sexual partners and travelers.

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