2.1 Introduction

Zika virus (ZIKV) is usually transmitted to humans by Aedes mosquitos [38,39] but is also transmittable sexually [40], congenitally [41–43], and by blood transfusion [44–46]. Most infections are asymptomatic, but about 20% of infected persons develop mild febrile illness [46–48]. The Zika epidemic of the Americas beginning in 2015 remains the largest outbreak to date. In response, the U.S. Food and Drug Administration (FDA) briefly discontinued blood collection in Puerto Rico in February 2016 [49], requiring blood to be imported until universal individual donation nucleic acid testing (ID-NAT) was operationalized in March 2016 [50]. In August 2016, the FDA began requiring universal ID-NAT for ZIKV in the 50 states and Washington, DC, and implementation was phased in over 12 weeks [51].

The FDA’s decision was motivated by several factors, including the well-documented transfusion transmission of related flaviviruses [52–55], reports of transfusion-transmitted ZIKV (TTZ) [45], and emerging evidence of rare but severe sequelae that include Guillain–Barré syndrome [56–58] and congenital Zika syndrome. Congenital Zika syndrome can result in severe birth defects, such as microcephaly [43,59,60]. During the first year of donation testing in the United States, universal ID-NAT resulted in the interception of 257 donations positive for ZIKV RNA in Puerto Rico and 54 in the 50 states (AABB. Personal communication.) [61].

One study estimated the cost of universal ID-NAT to be $137 million annually in the 50 states and Washington, DC [34], and another estimated that the American Red Cross spent $5.3 million per ZIKV-positive donation interdicted by ID-NAT in the 50 states during June 2016 through September 2017 [62]. Other countries have not followed the example set by the United States of screening for ZIKV, perhaps because of high cost and uncertain cost-effectiveness. Such concerns are particularly important when ZIKV screening is considered alongside alternative uses of limited health care resources.

In July 2018, the FDA issued revised guidance recommending universal mini-pool NAT (MP-NAT) with triggers to ID-NAT during local autochthonous or travel-acquired outbreaks, similar to strategies currently used for West Nile virus (another mosquito-borne infection for which donations are universally screened) [63]. In this study, we estimated the effectiveness and cost-effectiveness of universal ID-NAT, universal MP-NAT, and alternative ZIKV screening policies by simulating the costs and clinical outcomes in 2 settings, Puerto Rico and the 50 states.