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Individual Testing Effective, But Costly,
in Screening for Zika Virus in Blood
Donations
In March 2016, approximately one
year after Zika virus (ZIKV) infections
were reported in the United States, the
U.S. Food and Drug Administration
(FDA) recommended that states and
territories convert from mini-pool
screening to individual-unit screening
to minimize the risk of ZIKV trans-
mission through blood components.
In an investigational screening
study published in The New England
Journal of Medicine, researchers noted
that the use of one such testing method
– an individual transcription-mediated
amplification (TMA) for RNA testing
– is costly and provides a low yield.
This assay, although highly accurate for
testing for ZIKV, may not be economi-
cally feasible in the real-world setting,
compared with the standard practice
of screening donors with risks of ZIKV
infection based on geographic areas
with the greatest risk.
Of more than 4 million samples
analyzed in the study, “ZIKV RNA
was detected for the nine donors
whose infection came from a mos-
quito bite and was present in plasma
and red cells for long periods of
time,” lead author Susan L. Stramer,
PhD, vice president of scientific af-
fairs at the American Red Cross, told
ASH Clinical News. “Importantly,
of the nine confirmed positives,
ASHClinicalNews.org
the three donations that were most
likely to result in transmission were
detected by mini-pool nucleic acid
testing, as well as individual donation
nucleic acid testing.”
To evaluate the accuracy and
feasibility of individual nucleic acid
testing, researchers at the American
Red Cross screened a total of
4,325,889 blood donations from five
southeastern states considered high
risk for ZIKV development (Alabama,
Florida, Georgia, Mississippi, and
South Carolina) between June 2016
and September 2017.
They retested initial reactive
donations to establish ZIKV pres-
ence, then confirmed ZIKV presence
using repeat TMA, TMA testing in
exploratory mini-pools, real-time
reverse-transcriptase polymerase
chain reaction, immunoglobulin
(IgM) serologic testing, and red-cell
TMA.
Of the donations individually test-
ed during the 15-month study period,
investigators identified 160 samples
as initially reactive (n=160) and
4,325,729 samples as non-reactive.
Six of the initially reactive dona-
tions were also reactive on repeat
TMA, with four donations confirmed
as IgM-negative. Of the 154 samples
that registered as non-reactive on
repeat testing, three were later con-
firmed IgM-positive, for a total of
nine confirmed positive samples.
That translated to a “confirmed-
positive rate” of one for every 480,654
samples, with a positive predictive
value of 5.6 percent and a specificity
of 99.9 percent.
Transmission of the virus in nine
donors was likely attributable to:
• locally transmitted infections in
Florida (n=2)
• travel to ZIKV-active areas (n=6)
• receiving an experimental ZIKV
vaccine (n=1)
In the ZIKV-positive samples, the
levels of ZIKV RNA varied depend-
ing upon where they were detected:
• red cells: 40-800,000 copies/mL
up to 154 days following dona-
tion
per ZIKV RNA–positive donation,
making it economically unfeasible.
“Clinicians should know that
blood is safe and no transfusion-
transmitted ZIKV infections have
occurred in the U.S.,” she noted. “In
fact, only four recipients have been
documented to have been infected
from transfusion (all in Brazil), and
these four recipients were transfused
with blood products from three
infected donors.” Following transfu-
sion, said Dr. Stramer, none of these
recipients developed symptoms as-
sociated with ZIKV RNA.
Based on these results, she
believes that “the conversion to
mini-pool nucleic acid testing from
individual donation nucleic acid
testing, as required by the FDA today,
would be a better use of resources
with equivalent patient safety.”
However, this analysis was limited
by the lack of a comparator group,
which could have been used to deter-
mine superiority over other testing
modalities. In October 2017, the
FDA approved the cobas Zika test to
screen for ZIKV, which analyzes RNA
and plasma from individual donors.
The findings should also inform the
blood-screening recommendations
for other transfusion-transmitted
risks. “Clinicians should be educated
about the mitigation of other viruses
through transfusion, particularly from
Babesia microti, a red cell parasite
transmitted by the same tick as Lyme
disease,” Dr. Stramer said. Screening is
not yet required for this virus, despite
it posing “a far more significant threat
in parts of the U.S. where the ticks are
common, represented by more than
200 transfusion transmissions.”
“Tests that detect a broad range of
mosquito-borne agents are needed,
and clinicians should be aware that
there are other mitigation methods
besides testing, such as pathogen
inactivation,” she concluded.
The American Red Cross and
Grifols Diagnostic Solutions sup-
ported this study.
The authors report financial sup-
port from the American Red Cross.
REFERENCE
Saá P, Proctor M, Foster G, et al. Investigational testing for Zika
virus among U.S. blood donors. N Engl J Med. 2018;378:1778-88.
• plasma: 12-20,000 copies/mL up
to 80 days following donation
Overall, the authors calculated that the
costs of identifying eight mosquito-
borne ZIKV infections through
individual screening was $5.3 million
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