Times to Key Events in the Course of Zika Infection and their Implications for Surveillance: A Systematic Review and Pooled Analysis

Abstract

Background Evidence suggests that Zika virus has driven a 10-fold increase in babies born with microcephaly in Brazil, prompting the WHO to declare a Public Health Emergency of International Concern. However, little is known about the natural history of infection. These data are critical for implementation of surveillance and control measures such as protecting the blood supply. Methods We conducted a systematic review and pooled analysis to estimate the distribution of times from Zika infection to symptom onset, seroconversion, and viral clearance, and analyzed their implications for surveillance and blood supply safety. Results Based on 25 case reports, we estimate the median incubation period of Zika virus infection is 5.9 days (95% CI: 4.4-7.6), and that 95% of cases will develop symptoms by 11.1 days post-infection (95% CI: 7.6-18.0). On average seroconversion occurs 9.0 days (95% CI, 7.0-11.6) after infection, and virus is detectable in blood for 9.9 days (95% CI: 6.8-21.4). In 5% of cases detectable virus persists for over 18.9 days (95% CI: 12.6-79.5). The baseline (no screening) risk of a blood donation being infected with Zika increases by approximately 1 in 10,000 for every 1 per 100,000 person-days increase in Zika incidence. Symptom based screening reduces this by 7% (RR 0.93, 93% CI 0.86-0.99), and antibody screening by 29% (RR 0.71, 95% CI: 0.28-0.88). Conclusions Symptom or antibody-based surveillance can do little to reduce the risk of Zika contaminated blood donations. High incidence areas may consider PCR testing to identify lots safe for use in pregnant women.