Conference Coverage

Zika virus testing shows low incidence in donor blood outside of high-infection areas


 

AT AABB17

SAN DIEGO– The Zika virus is primarily transmitted via the Aedes mosquitoes, most commonly by A. aegypti, but recent outbreaks have revealed that nonvector transmission routes may also spread the infection. Some data suggest that blood transfusion can be a source of transmission.

While the number of contaminated blood donations remains very small, three studies presented at the American Association of Blood Banks annual meeting confirmed the ability of new investigational assays to detect Zika virus in donated blood.

There have been no confirmed transfusion-transmission cases of Zika virus in the United States, but as cases have now been documented in Brazil, the Food and Drug Administration issued revised guidance in August 2016 recommending that blood centers in all states and U.S. territories screen individual units of donated whole blood and blood components.

Zika test tube copyright Felipe Caparrós Cruz/Thinkstock

In the first report (C7-A01C), Paula Saá, PhD, and her colleagues at the American Red Cross initially investigated the use of mini-pool (MP)- nucleic acid testing (NAT) using the Procleix Zika Virus Assay (TMA). Testing was initially implemented on blood collections from Florida, Georgia, South Carolina, Mississippi, and Alabama – five states that were presumed to be at high risk of Zika virus infection. After the FDA revised its guidance, the protocol changed and testing was extended to all blood donations. The use of the MP-NAT was also converted to individual donation (ID)-NAT, and questions concerning travel history was also eventually discontinued.

However, even with the use of ID-NAT, the rate of confirmed positive donations was quite small but the associated cost was quite high, the researchers pointed out. “In the first year of testing at the American Red Cross, we identified nine confirmed positive donations,” said Dr. Saá.

The rate of confirmed positive donations was 1:354, 602 during the study period, but if the period up until September 2017 is taken into account (no additional cases were identified), the rate increases to 1:514,266. “This is a very low rate,” Dr. Saá said. “If there are no changes to the current guidelines, we have estimated that the yearly cost for the American Red Cross of testing will exceed $48 million.”

These figures extrapolate to approximately $6 million per confirmed case, according to the results of this study sponsored by the American Red Cross.

Confirmatory testing included repeat TMA; in addition, RT-PCR, serology and red blood cell count (RBC) TMA were performed. Estimates of viral loads were performed by endpoint TMA on plasma and RBCs.

A total of 2,288,855 blood donations had been tested as of April 2017, including 393,713 (17%) in 24,611 MPs, which did not detect any reactive donations.

Of the confirmed positive blood donors, three lived in Florida and two of those were from local transmission. Six individuals had traveled to a region highly active for Zika virus, and returned to the United States between 2 and 73 days before donating blood. Clinical symptoms were reported in two individuals with a travel risk; the other donors with a confirmed positive test (75%) remained asymptomatic. The longest period for detection in RBCs was 91 days thus far, but in the same person, detection in plasma was only 17 days.

“The data that we are showing here recommends a testing strategy with mini pool testing in areas at low risk of Zika transmission,” said Dr. Saá.

A second related study (C9-A01C), described the detection of ZIKV RNA in blood donations collected in U.S. states between April 3, 2016, and September 23, 2017, using the cobas Zika test, to be used on the cobas 6800/8800 Systems.

Although the test was investigational during the study period, it has just been approved by the FDA, said study author Lisa Pate, MD, who is with Roche Molecular Systems, the manufacturer of the cobas Zika test and cobas 6800/8800 systems. “This is now the first licensed test for screening blood donations for Zika virus.”

Overall, testing showed that Zika contamination in the U.S. blood supply was quite low. Only 0.001% of screened blood donations in United States were confirmed as true positives.

The development of this test came about after the first cases of Zika virus in the United States were detected in Puerto Rico in December 2015, explained Dr. Pate. Shortly after that, the FDA issued guidance prohibiting the use of blood collected in Zika active areas, unless the donations were screened.

“The impact was significant in Puerto Rico, as blood donations were halted, which then forced Puerto Rico to rely on imported blood,” she said.

About that time the FDA reached out to Roche and competitors to see if a test could be developed to screen for Zika.

The cobas Zika test was approved under an investigational new drug application on March 30, 2016, and although initially used to test blood samples in Puerto Rico, testing was expanded to include donor blood from all over the country.

Screening was conducted by individual donation testing, with all initial reactive results repeated in duplicate. Supplemental testing was also done, and included an alternative NAT (AltNAT) assay which was considered to be less sensitive than cobas Zika and serology testing for anti-Zika IgM and IgG. A donor confirmed Zika confirmed positive if at least one replicate of the repeat testing by cobas Zika was reactive on index donation or follow-up, reactive by AltNAT on the index donation, or positive for anti-Zika IgM on index or follow-up.

Screening was conducted at 12 testing labs in the United States, and more than 4 million donations were screened and 27 positive donations were confirmed. Overall, that amounted to less than 1 in 100,000.

“For donors in the U.S. with confirmed positive results, and for whom follow-up information is available, 84% of them report recent travel to Zika active areas,” noted Dr. Pate.

For Puerto Rico, 111,842 blood donations were screened and there were 356 confirmed positive results. The incidence is much higher than in United States, and was 1.27% during peak incidence in July 2016.

A third paper (C12-A01C), also reported on testing the blood supply in Singapore, which had reported its first locally transmitted Zika case last August, using the investigational Procleix ZIKV nucleic acid technology (NAT) assay.

The presence of Zika virus in screened blood was also quite low, with an incidence of only 0.0032%. The Procleix ZIKV assay was found to suitable for screening for Zika infection in an asymptomatic population, as it showed good analytical sensitivity and clinical performance.

The Zika virus came to Singapore in May 2016, imported by an individual who had recently traveled to Brazil, said Sally Lam, laboratory director, Blood Services Group, Health Sciences Authority, Singapore.

“Then in August we had 41 confirmed local Zika virus cases,” she said.

In 2016, there were 458 clinical Zika cases reported, with 8 clusters identified. This year, 63 cases have been reported to date, she said.

Mandatory Zika virus screening in donor blood with ID-NAT began after the onset of local outbreaks, and was implemented in January 2017. A total of 126,906 blood donations were screened.

Researchers in Singapore assessed the performance of the Procleix ZIKV NAT assay for universal blood donation screening. They screened all blood that was donated, beginning Oct. 1, 2016, a confirmed case was defined as having Zika RNA by PCR and/or Zika antibodies. Analytical sensitivity was assessed by use of 300 blinded frozen samples containing Zika virus and 25 negative controls. The performance of the Procleix ZIKV assay was also evaluated by use of samples from the local patient population.

Of four confirmed positive cases, only one was available for follow-up. “In the index donation, the viral load was quite high in the plasma but at 10 days, it was reduced to about 400 copies/mL in the plasma,” said Ms. Lam. “The donor did not develop any symptoms.”

The analytical sensitivity for the Procleix ZIKV assay was determined to be 2.1 copies/mL at 50% LOD and 10.0 copies/mL at 95% LOD, and it detected RNA in six out of nine patient samples for an 85.7% agreement with reference material, according to the researchers.

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