CDC, NIH lab lapses with deadly agents lead to calls to halt research
IPs should assess lab safety in light of incidents
By Gary Evans, Executive Editor
A recent series of stunning lapses and oversights in federal research labs working with deadly pathogens and potential bioterror agents has heightened calls for a moratorium on such research until biosafety and security can be assured.
"Such incidents have been accelerating and have been occurring on average over twice a week with regulated pathogens in academic and government labs across the country," a group of scientists and researchers warned in a position statement on the issue." An accidental infection with any pathogen is concerning. But accident risks with newly created potential pandemic pathogens’ raise grave new concerns." (See related story p. 89) The agents involved — anthrax, highly pathogenic H5N1 avian flu and, astoundingly, smallpox — were as shocking as the top tier federal agencies that mishandled them: the Centers for Diseases Control and Prevention and the National Institutes of Health.
While the incidents involved research labs, infection preventionists can seize the highly publicized events as a "teachable moment" to review practices and biosecurity with their clinical lab colleagues.
"Even though lab personnel most likely knew about [these lab breaches] at the same time as IPs from their professional associations, I think sharing the incident would be a moment to bond even more with some of our number one infection prevention partners," says Patti Grant, RN, BSN, MS, CIC, an infection preventionist at Methodist Hospital for Surgery in Addison, Texas. "It is frightening, but it is always great when an opportunity arises where we can discuss a mutual topic outside of our daily work routines."
Though a safety review would be wise in any case, some may argue that hospital clinical labs would never deal with such pathogenic agents. True enough in the main, but as recent incidents with MERS and other pathogens demonstrate, an infection of any etiology from anywhere in the world can show up unannounced in any given U.S. emergency department. To precisely that point, the CDC recently released patient isolation guidelines for Ebola for U.S. hospitals, emphasizing the need for basic preparation in case a traveler infected in the ongoing outbreak in West Africa is admitted for treatment. (See relatedly story p. 90)
"I would hope that — if these kinds of incidents can take place at the CDC — that every laboratory director would take this as an opportunity to take a time out and review their own laboratory safety policies and procedures," says William Schaffner, MD, chairman of the Department of Preventive Medicine at Vanderbilt University Hospital in Nashville. "This is another example that human beings don’t get it right all the time. We have to guard ourselves against ourselves."
A troubling trifecta
After lab incidents involving anthrax and H5N1 avian flu occurred at the CDC, the NIH completed the trifecta by reporting that six long-forgotten vials of smallpox were discovered in a lab cold storage area. The sealed glass ampules had been apparently sitting in a box, buffered in cotton, since the 1950s.
"I could not believe that when I heard it," Schaffner says. "At least 2 of the six vials have grown live smallpox. There have been some further explanations that this was the kind of storage area that [the NIH] had not anticipated that anyone would ever have put smallpox virus in to."
With smallpox eradicated in the wild in 1980, the vaccine is no longer routinely administered and much of the planet’s population would be susceptible to the variola virus — a disfiguring killer that plagued human kind for centuries. (See smallpox story, p 89.)
Before breaking down the details of the anthrax and H5N1 incidents, it should be noted that the CDC has issued a strong response to the incidents that included forming a new expert advisory committee on laboratory practices and safety to provide expertise and oversight.
"CDC director Tom Frieden has taken responsibility and very forthrightly has looked at this as a CDC-wide potential problem and instituted a series of corrective actions," Schaffner says. "I think when these are fully implemented it will restore the CDC to its justified role of primacy in the public health lab area. Not only in the United States, but around the world."
One approach that should be considered in labs is the kind of checklist or "time out," approaches that have proven effective in health care and other industries, he adds.
"We are terrifically reassured that pilots — each and every flight — have to go through a check list before the plane pulls away from the gate," he says. "In surgery we now have instituted time outs. Everybody stops and reviews exactly what the surgery is going to be. They actually put a mark where the surgery is going to take place so we don’t take out the left kidney when we meant to take out the right. These events have happened in the past and now we have simple, rigorous procedures to preclude that from happening. They all have to be adhered to rigorously whether you are doing surgery, flying a plane, or working in a laboratory. Clearly, these kind of checklists and timeouts need to be put in place at the CDC."
Anthrax and avian flu incidents
The anthrax incident at the CDC began on June 5, 2014 when a laboratory scientist in the Bioterrorism Rapid Response and Advanced Technology (BRRAT) laboratory prepared extracts of Bacillus anthracis under biosafety level (BSL) 3 containment conditions. The purpose was to render the pathogen non-infectious so it could be used to evaluate a method of rapid identification of anthrax, which would help considerably in dealing with false "white powder" events which have caused chaos since the 2001 anthrax mail attacks.
However, the lab scientist used a modified protocol and tested the anthrax for viability at 24-hours rather than the recommended 48. No growth on any of the 16 plates was observed at 24 hours, but it would be later discovered that live anthrax remained. Not just any live anthrax mind you, but the notorious Ames strain that killed five people and infected 17 others in the 2001 mail attacks. This was discovered after a few days of experiments had already been conducted in two step-down labs, where workers thinking they were dealing with inactivated anthrax were like so many unprotected electricians wiring circuits and switches after being assured that the main power was off. Dozens of CDC workers were potentially exposed, particularly since there was concern that one of the lower lab procedures "agitated" the anthrax and could have aerosolized the pathogen. Ultimately no one was infected, but the incident was nerve wracking for all involved.
"We’re very concerned about the health and well-being of our own staff," CDC Director Tom Frieden, MD, said at press conference. "The fact that they had to deal with uncertainty, stress, potential risk and to take preventive medicines that can have adverse effects as a result of this incident is something that I feel terrible about."
A CDC report found the primary contributing factor to the incident was the lack of an approved, written study plan reviewed by CDC senior staff to ensure that the research design was appropriate and met all laboratory safety requirements. The report also noted the following other contributing factors: use of unapproved sterilization techniques; transfer of material not confirmed to be inactive; use of live anthrax inappropriate for this experiment; inadequate knowledge of peer-reviewed literature related to inactivation of anthrax; and lack of a standard operating procedure or process to document inactivation in writing in the BRRAT lab. In the wake of the incident the director of the BRRAT lab, Michael Farrell, PhD, submitted his resignation, according to published reports.
Following the anthrax lab breaches, more than 80 CDC employees were offered post-exposure prophylaxis with a 60-day regimen of ciprofloxacin or doxycycline and/or the anthrax vaccine used by the military. However, the CDC occupational health response was beset by controversy as well, according to a damning independent investigation by the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS).
"There was no clear, single manager overseeing the overall CDC incident response, which resulted in employee confusion about how to manage the response to the incident," Jere Dick, PhD, associate administrator of the APHIS, testified at a July 16 Congressional hearing. "In addition, CDC’s Occupational Health Clinic was inadequately prepared to respond to the potential exposure of a large number of workers, resulting in some staff not knowing if they were at risk and at least one person who was in contact with contaminated material without proper personal protective equipment not being examined for 5 days."
Director kept in dark about flu incident
On the heels of the anthrax incident, reports surfaced that the CDC had sent a presumably low-pathogenic H9N2 avian influenza virus sample to a federal poultry research lab that was found to be contaminated with deadly avian influenza H5N1. The worst case scenario is fairly easy to imagine because H5N1 has a 60% mortality rate in humans. Again, no one was infected — in part because the receiving lab took necessary precautions instead of just assuming the flu was benign. In fact, the receiving lab — a USDA research facility at the University of Georgia in Athens — actually alerted the CDC that the shipment was contaminated with H5N1.
"At this point everything we’ve looked at strongly suggests that there was no exposure of anyone to influenza," Frieden said. "The people who were involved were wearing what are called PAPRs’ or positive air pressure respirators. They were working in an enhanced BSL-3 facilities [with] multiple redundant checks to prevent infection with flu."
Though the flu incident was bad enough, an aggravating factor that speaks volumes about the lab safety culture at the CDC is that Frieden was not notified of the incident until six weeks after it happened. In addition, the cross contamination of flu strains occurred in the influenza lab, a world class facility that is a point of pride at the CDC.
An unacceptable delay’
"For me personally, this is the most distressing of the [recent] incidents for two reasons," Frieden said at a July 11 press conference. "First, because it happened in our influenza laboratory. And second, because it happened six weeks ago, and I learned about it less than 48 hours ago."
The flu incident remained under investigation as this issue went to press.
"We’re still just beginning the investigation to determine how this happened," Frieden said. "The work was done in one room. So that leads to some early hypotheses of what might have happened. But it’s going to take a detailed investigation. And we may not know for certain exactly what happened, but we’ll do everything we can to find out."
In response to the incidents, the CDC shut down some labs and placed a moratorium on biological material leaving BSL-3 and BSL-4 laboratories until further notice. "We will assess laboratory by laboratory before reopening," Frieden said. Though no one was infected at either the CDC or the other lab, the incident was clearly disturbing to Frieden.
"The fact that something like this could happen in such a superb laboratory is unsettling because it tells me that we need to look at our culture of safety throughout all of our laboratories," he said. "[It is] deeply troubling that there was an unacceptable delay in providing this information. It’s very important to have a culture of safety that says if you’ve got a problem, talk about it. The biggest way to get into more trouble is not to talk about something when you’ve got a problem."
Among the other actions CDC is taking are a comprehensive review of its lab procedures and appointing a single point person to assess lab activities and report directly to Frieden. That person is Michael Bell, MD, a veteran medical epidemiologist and hospital outbreak investigator in the CDC Division of Healthcare Quality Promotion.
Work of safety is never complete’
"There’s some major systematic issues that we want to look at," Bell said at the press conference. "It’s not the little mistake that we’re concerned about in this instance. We’re concerned about what is the framework that everyone’s using? And that framework includes rapid reporting. It includes an understanding of the chain of communication and who you tell when.
"Add to that the fact that people need to be comfortable doing this," he added. "We can bolster that and make use of this series of events to make sure that in the future there is much less likelihood of this happening again. The work of safety is never complete. We will continue to innovate. We’ll be continuing to have new technologies. There will be new diseases. And this is part of the work that we do in public health to maintain safety and grow with the science so that we can assure that what we do doesn’t harm anybody that’s doing the work or is nearby."