While infections caused by the Zika virus captured the world's attention in 2016, much about the virus remains unknown, including the proportion of asymptomatic cases and the duration of the virus' presence in the blood, or viremia. In a report published in Blood, Pierre Gallian, of the Aix-Marseille UniversitÃ© and French Institute of Research for Development in France, and authors evaluated the prevalence of the Zika virus among blood donors from Martinique using epidemiologic, biologic, and clinical information, attempting to refine the characteristics of the Zika virus in adults.
"Estimating the prevalence of Zika infections is difficult because a large proportion of infected individuals do not seek medical attention and seroprevalence studies are hampered by antigenic cross-reactivity with other flaviviruses," Mr. Gallian and co-authors wrote.
Martinique, which includes the French West Indies, Caribbean region, is where Zika was recognized in late 2015. In response, the French Blood Bank implemented systemic individual Nucleic Acid Testing (NAT) of all blood donations during a five-month period to screen for Zika-contaminated blood donations.
Between January 19, 2016, and June 10, 2016, 4,129 consecutive blood donations were collected and tested. The blood donations came from patients with a mean age of 41.9 years, with a male/female sex ratio of 0.88.
Almost two percent of blood donations were found to be contaminated with Zika (n=76; 1.86%). The most intense detection rate (3%) occurred17 to 20 after exposure, and Zika-contaminated blood donations came from patients with a mean age of 41.8 years, with a male/female sex ratio of 1.2.
All patients also were contacted by phone seven days post-donation to identify symptoms compatible with Zika virus infection. If a donor did not report any symptoms, a new call was scheduled for 14 days post-donation.
Symptom information was collected from 75 donors found to have the Zika virus in their blood. Thirty-four of these donors (45.3%) were truly asymptomatic, and the proportion of cases that did not require medical attention was even higher. Forty-one donors reported symptoms (54.7%) one to six days post-donation, including fever, conjunctivitis, myalgia, arthralgia, and rash.
Men were less likely to report symptoms than women (45.2% vs. 66.7%; p=0.06), but viral load and time to declaration of symptoms were not significantly different.
Symptomatic donors had higher levels of molecular viral load, compared with asymptomatic donors (mean values: 5.36 vs. 4.3 log10 RNA genomic equivalents/mL; p=0.0013). "This difference does not imply that symptomatic donors reached higher viremia than asymptomatic donors," Mr. Gallian and authors noted. "Sampling could occur in the former only during the early steps of viremia, while in the latter, it could also occur during the decreasing phase of viremia."
The authors performed seroprevalence analyses, using an anti-Zika virus NS1 immunoglobulin G enzyme-linked immunosorbent assay kit, at two time periods: March 9 to 23 (n=418 donors) and June 6 to 13 (n=176). Zika-positive samples were further processed by microneutralization in a 96-well format. The seroprevalence after seroneutralization was 13.5 percent in March, then jumped to 42.2 percent in June.
During the same period, the cumulative curve of incident cases detected by NAT in blood donors was almost linear, the authors reported, prompting them to estimate that the duration of asymptomatic viremia is four to six days. This finding is consistent with the observation that the longest period reported between blood donation and symptoms (presymptomatic viremia) was six days.
The estimated number of clinically suspect cases in Martinique was approximately 7,600 in March (2% of the population) compared with approximately 28,900 in June (7.6% of the population). "With reference to seroprevalence results, this suggests that the proportion of cases [that] did not seek medical attention was 80 to 85 percent and did not change significantly along the study period," the authors wrote.
In August 2016, the U.S. FDA recommended universal testing of donated blood and blood components for the Zika virus in the United States. "Testing the entire blood supply will help ensure that safe blood is available for all individuals who might need transfusion," Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, said about the decision. The FDA also authorized the emergency use of several investigational Zika screening tests, as well as a pathogen inactivation technology that kills the virus in blood platelets and plasma.
"We suggest that, once the duration of asymptomatic viremia has been estimated (e.g., from early analysis of seroprevalence and PCR detection datasets), NAT incidence studies in blood donors could improve prevalence estimates in the general population in the case of disease with frequent mild or asymptomatic clinical presentations such as Zika fever," the authors concluded.
Gallian P, CabiÃ© A, Richard P, et al. Zika virus in asymptomatic blood donors, Martinique: 2016. Blood. 2016 November 8. [Epub ahead of print]