Documents reveal intense battle over CDC Zika tests
A protracted battle between a Zika expert at the U.S. Centers for Disease Control and Prevention (CDC) and his superiors over tests for the virus came to light yesterday.
The fracas centers on allegations by CDC’s Robert Lanciotti, chief of the Diagnostics and Reference Laboratory Activity for mosquito-spread viruses in Fort Collins, Colorado. He alleges that the agency’s Emergency Operations Center (EOC) discounted his research in April 2016 and created “a public health threat” by relying on a less dependable human test for the Zika virus
As first reported by the The Washington Post, Carolyn Lerner, who heads the U.S. Office of Special Counsel, wrote President Barack Obama a detailed letter yesterday about the allegations. She also released several related reports, including an investigation conducted by the Department of Health and Human Services, and Lanciotti’s response. Lerner became involved after Lanciotti was demoted for his actions in May and filed a whistleblower suit. Her office “secured an agreement” with CDC to reinstate him as head of his lab.
At the heart of the dispute is the fact that, in some people who become infected with Zika, viral levels in the blood remain relatively low, making the virus difficult to detect. Lanciotti alleged that a Zika test made by his lab, called Singleplex, was more sensitive than another test he initially helped devise, called Trioplex (which also tested for the related dengue and chikungunya viruses). Both tests rely on the polymerase chain reaction to amplify minute amounts of viral RNA. But Lanciotti said comparison tests in his lab, and a study conducted independently by the Blood Systems Research Institute in San Francisco, California, found that Trioplex failed to detect viral DNA in up to 39% of samples that the Singleplex test had indicated contained Zika.
Officials at EOC, however, had confidence in the Trioplex test. They said it performed equally well as Singleplex in a comparative analysis conducted in a CDC lab in Puerto Rico.
Concerned that state labs would abandon Singleplex for what he saw as the inferior Trioplex, Lanciotti on 21 April emailed 30 state labs, telling them that his lab was continuing to use Singleplex “due to its greater relative sensitivity.” One of the leaders of the EOC lab team told the HHS investigators that Lanciotti’s email "created more trouble and confusion than it clarified."
The HHS investigation team, which did not include CDC employees who worked in EOC or in the zoonotic infectious diseases branch, concluded on 2 September that evidence did not support Lanciotti’s allegations about Singleplex’s superiority, or that there was any specific danger to public health because of the use of Trioplex. The tests conducted in Puerto Rico, the report states, “produced the clearest, most complete, and most reproducible data available to the investigative team, [and] found no difference in sensitivity.” Even if data showing superiority of Singleplex were accurate, the investigators say the 39% “overstates the potential impact” of missed cases; clinicians use the test as only one indicator when making a Zika diagnosis, and if that’s factored in, the missed cases drop to a maximum of 12% even with the most discrepant tests. What’s more, only Trioplex was granted what’s known as “emergency use authorization” by the U.S. Food and Drug Administration.
In addition to a lack of convincing evidence that Trioplex was inferior in comparative analyses, the investigators noted that the test was modified in August to include larger samples of blood or urine, as well as whole blood—all of which should contain higher levels of the Zika virus, making it easier to detect.
In a stinging rebuttal Lanciotti submitted 15 September, he wrote that CDC needed to reevaluate the “entire EOC concept,” which he said relied on “relatively inexperienced individuals making critical decisions.” He stressed the Trioplex test also performed poorly in detection of the four different dengue virus strains in circulation. And he further criticized EOC for promoting “a questionable assay with misleading communications” and for not having “greater transparency.”
Lerner’s letter stressed that “Lanciotti raises serious concerns about each of the CDC's findings, including the methodology for discounting his research,” but she said the “matter is now closed.”