Lanciotti was demoted in May after he raised concerns inside and outside the agency about the CDC’s decision in the spring to recommend a new test for Zika. That test is substantially less effective than another established test, he said, and misses nearly 40 percent of Zika infections. He also said the agency withheld information about testing differences from state and local public health laboratories.
The scientist was reinstated to chief of his lab in July after he filed a whistleblower retaliation claim, according to documents made public Tuesday by the Office of Special Counsel, an independent federal watchdog agency that handles whistleblower complaints.
The questions raised by Lanciotti prompted an internal investigation by the CDC. Its report was among the documents released Tuesday, when a review of the investigation was sent to the White House and Congress.
CDC investigators acknowledged in their report that testing for Zika is difficult and needs to be improved. The agency said it made improvements that will boost the new test’s sensitivity, according to the CDC’s investigative report. The internal investigation also found that the CDC acted reasonably when it withheld the conflicting test data from state public health labs. Releasing it could have created “considerable confusion during an ongoing emergency response,” the investigators said.
The issues raised in the debate illustrate the challenges of managing one of the world’s biggest public health crises at a time when the agency's urgent requests for emergency funding have been held up in Congress. Additional research funds could potentially have allowed for more extensive study of the tests and how best to implement them. In particular, the debate shows the pressure the CDC was under to quickly develop an accurate diagnostic test for a disease that is still poorly understood.
In a statement late Tuesday, the CDC said it had conducted a thorough independent investigation and determined the allegations were not substantiated by the evidence. The agency said it remains committed to providing its public health partners with the best available science and tools to combat the epidemic. The agency also "continues to strengthen the Trioplex test," including an update to the test’s instructions to strengthen its performance.
"Still, we need simpler quicker tests. To date, HHS has obligated more than $20 million toward the development of diagnostic tests for Zika," the CDC said. "This is a critical area of research for which additional funding from Congress is essential."
Many state and local labs have a backlog of samples to be tested for Zika. The problem is particularly urgent for pregnant women because Zika can cause severe defects in developing fetuses. The tests in question are the first of three types of tests for Zika exposure, so there is little chance people were ultimately misdiagnosed, according to the CDC.
During a 2007 Zika outbreak in Micronesia, Lanciotti’s lab developed a test to detect traces of the Zika virus in a person’s blood. Called the Singleplex, it detects genetic material up to seven days after onset of illness.
When the Zika outbreak hit Brazil, this test, and another one also developed by Lanciotti’s lab to detect antibodies the body makes to fight infections, were used on samples submitted to the CDC for diagnosis.
Determining whether someone has been infected with Zika is enormously difficult because most infected people don’t have symptoms. And many countries in South and Central America and the Caribbean hard hit by Zika have also had outbreaks of two related viruses — dengue and chikungunya — that officials worried could be confused with Zika.
Last fall, scientists at CDC’s dengue branch lab in Puerto Rico began work on a diagnostic tool that would detect all three viruses in one test. Lanciotti warned that combining the three might reduce their individual sensitivities. The original goal was to develop a test and conduct extensive evaluation necessary for approval by the Food and Drug Administration to market the test.
But by the end of last year, the worsening Zika outbreak “increased the urgency to quickly develop an assay,” CDC investigators found. The virus was spreading quickly, and there was increasing evidence linking the virus to severe birth defects. In March, the CDC sought emergency FDA approval to allow the new test to be distributed to state and local public health labs. One day later, on March 17, the FDA approved emergency use of the test, called Trioplex. Shortly thereafter, the CDC notified public health labs about the test and began shipping it.
Lanciotti compared the two tests and found that the Trioplex missed 39 percent of Zika infections that were detected by the Singleplex. An independent laboratory came to a similar conclusion. But a study by the CDC lab in Puerto Rico found no difference in sensitivity. CDC investigators said they were unable to reach a “statistically-valid conclusion about the relative performance” of the two tests.
Within the agency, “there was extensive communication, debate, analysis and discussion” about the performance of the two tests, according to the CDC investigators. CDC officials decided the difference between the two tests was not conclusive.
Lanciotti disagreed with the decision and in mid-April, he emailed his contacts at about 30 public health laboratories. He notified them that his own lab at Fort Collins was continuing to use the Singleplex instead of the Trioplex because of its greater relative sensitivity “that we have just established/became aware of through comparative analyses in several laboratories.”
The email caused confusion among state labs and apparently angered some other CDC officials who did not know that Lanciotti had sent the email. One official told Lanciotti his email “created more trouble and confusion than it clarified.”
The CDC notified the state labs about which tests were recommended in the Zika response but did not address the differences in performance directly. The agency said the low level of Zika virus in the blood could “pose a challenge” for molecular testing and said it was continuing to evaluate the performance of its tests.
Lanciotti remained “deeply concerned with what he viewed as CDC’s promotion of an inferior” test, according to CDC investigators. In mid-May, he emailed senior CDC leaders and asked again that the test’s lesser sensitivity be shared with public health laboratories, accusing the CDC of deliberately withholding information.
A week later, he was reassigned to a nonsupervisory position.
In late August, the CDC made several changes to improve the test's sensitivity, such as authorizing laboratories to use larger volumes of blood that would contain more virus and make the evidence easier to detect.
In his response to the CDC investigation of his complaint, Lanciotti acknowledged that the agency’s improvements to the new test may increase its sensitivity. But, he noted, that action happened four months after he first raised the issues.
In the report released Tuesday, special counsel Carolyn Lerner noted that Lanciotti “raises serious concerns about each of the CDC's findings,” including the methodology the agency used to discount findings that the new Trioplex test “may detect fewer Zika infections” than the established test.
She urged the CDC to respond to his concerns and use his expertise as the agency “works to ensure it is implementing the most effective testing methods” in its Zika response. She added: “I also encourage the CDC to promote scientific debate within its labs. Whistleblowers should be encouraged to speak out on matters of public concern.”
This post has been updated.