​Although laboratory practice has changed dramatically since 1988, the widespread anxiety roused by the 2014-15 West African Ebola pandemic is not unlike that surrounding HIV in the 1980s.

By Nancy Maddox, MPH, writer

From today's vantage point, it seems like a long time ago. But the danger was real . . . and so was the fear.

In fact, one of every three laboratory workers surveyed at the annual meeting of the New Jersey Society for Medical Technology reported that they were considering leaving the profession because of fears stemming from the latest deadly disease to emerge from Africa. Just 43% of all respondents (91 of 212 meeting registrants surveyed) indicated that, in retrospect, they would have chosen a career in medical technology, knowing they would be required to handle specimens from patients infected with such dangerous bugs.

The year of the survey? 1988.

The bug in question? HIV.

Although laboratory practice has changed dramatically since 1988, the widespread anxiety roused by the 2014-15 West African Ebola pandemic is not unlike that surrounding HIV in the 1980s.

"When I was reading about fears people had doing Ebola testing, it reminded me of those [early days of the HIV pandemic]," said Mike Pentella, PhD, D(ABMM), director of the Bureau of Laboratory Sciences at Massachusetts' Hinton State Laboratory Institute.

For instance, in Texas—where the first patient diagnosed with Ebola in the United States was treated—The Dallas Morning News reported, ". . .  we learned a lot about the chaotic, reason-eroding effects of pure, unharnessed panic."

In the face of such strong emotions, many hospital laboratories refused to run blood tests on possible Ebola patients. As reported by the College of American Pathologists, a 2014 survey of the Compass Group (comprising 28 not-for-profit US healthcare systems) found that just four of 17 respondents allowed suspected or confirmed Ebola specimens into their hospital laboratories.

CDC found that, in some cases, alternate patient diagnoses were hampered because routine lab tests (e.g., serum chemistries and complete blood counts) were deferred until after Ebola infection was ruled out in at-risk patients. At least two people who tested negative for Ebola died from other causes.

But fear is not the only similarity between HIV and Ebola. Both pathogens are responsible for changing laboratory practice in important ways.

HIV, for example, can be credited with the introduction of recommended universal precautions in the 1980s to prevent contact with patients' blood and other bodily fluids and with the issuance of the federal Bloodborne Pathogens Standard. That standard, which took effect in 1992 and was updated in 2001, codifies the use of universal precautions and requires designated employers to implement plans to prevent worksite expo-sure to bloodborne pathogens via engineering controls (e.g., needleless medical devices), work practices (e.g., proper disposal of contaminated sharps) and personal protective equipment (PPE), such as gloves and goggles. It also mandates that employers use warning labels to identify hazards and provide at-risk workers with bloodborne pathogens training and hepatitis B vaccination.

The strategy proved enormously effective: CDC documented 52 cases of confirmed occupational HIV transmission through the end of 1999, but just a single case since then.

Ebola is continuing the laboratory transformation, with an emphasis on biosafety to safeguard workers, biosecurity to safeguard dangerous biological materials and quality management systems to assure continuous reevaluation of control measures. Or, to use the popular shorthand, Ebola is one more impetus—albeit a big one—for enhancing the culture of safety in the laboratory.

Said Pentella, "We have to remember how far we've come in our knowledge [of how to prevent worksite] transmission. . . I think we are making progress. . . . And it's real important for us not to lose our memory of the challenges we were facing with HIV, because it will make it harder for us to stay on task."

A False Sense of Security

One measure of the heightened seriousness accorded to laboratory biosafety and biosecurity is funding. CDC, still recovering from its own biosafety mishaps, created a new position dedicated to the issue—associate director for laboratory science and safety. (See related story on page 14.)

And, included in Congress's $5.4 billion emergency Ebola response package, passed in late 2014, was roughly $250 million for CDC to support state and local Ebola preparedness. A total of $145 million in supplemental funding was disbursed to 62 Public Health Emergency Preparedness (PHEP) cooperative agreement awardees—health departments in the 50 states, four major US metro areas and eight US territories and freely associated states (FASs)—with the stipulation that "public health agencies must ensure their jurisdictions have the ability to quickly, safely and accurately perform laboratory testing on suspected Ebola virus specimens."

Another $105 million or so went to current Epidemiology and Laboratory Capacity (ELC) grantees—health departments in the 50 states, six largest US cities and eight FASs—for several activities, including designating and training a full time biosafety officer (funded for three years), conducting a risk assessment to assure the laboratory can safely handle and dispose of Ebola and other highly infectious agents, and providing technical assistance to strengthen biosafety practices in local clinical labs.

In spring 2015, CDC awarded APHL a $2.2 million cooperative agreement to provide biosafety and biosecurity expertise and training to the newly funded public health laboratories and to develop materials to assist those laboratories with outreach and training for the sentinel, clinical labs in their jurisdictions.

"What we saw during the Ebola pandemic," said Chris Mangal, MPH, director of APHL's Public Health Preparedness and Response Program, "was significant variability in biosafety and biosecurity practices from laboratory to laboratory, and especially significant gaps in clinical labs. What we're hoping to do with our new CDC funding is to help strengthen those practices across the board."

One priority is training in specimen packaging and shipping for clinical laboratorians. Mangal noted that in New York City, where a physician was diagnosed with Ebola after returning from Guinea, the city public health laboratory sent its own staff to local hospitals to package suspect Ebola specimens and ensure safe shipment to the public health laboratory for analysis. "For this scenario, it worked in New York City," she said, "but it may not work again with a high volume of samples or especially in large states, such as Texas or California."

A second priority is improved risk management in all laboratories.

Reynolds ("Ren") Salerno, PhD, a senior manager at Sandia National Laboratories and co-editor of the newly published book, Laboratory Biorisk Management, advocates a fundamental shift in the way laboratories handle safety and security issues.

"Biology and the practice of biology have become much more complicated and diverse over the past 30 years," he said, "yet we're relying on a biosafety construct created in the early 1980s. I don't think it's adequate any longer."

Salerno, who left Sandia in early 2016 to lead CDC's Division of Laboratory Systems, promotes a substantive risk management process, defined by the acronym AMP, which stands for assessment, mitigation, performance.

The first, and in Salerno's view, most important, part of the process is a thorough risk assessment. He said, "Some of those risks may be biolog-ical, the risk of accidental infection inside the laboratory; containment risks, the possibility that a disease agent might escape from laboratory and contaminate an animal or human outside the lab; biosecurity risks, the risk that someone may want to misuse or steal materials from the laboratory; natural or environmental risks, hurricanes or earthquakes or tornadoes; operational risks that may make the laboratory unusable at a time when the population desperately needs laboratory services."

Next come control measures to mitigate risks to acceptable levels. And lastly is performance evaluation to determine the adequacy of control measures — essentially a system of continuous quality improvement.

The problem, Salerno said, is that the current system defers the risk assessment to national guidance: "We've assumed that a smart person sitting in Washington or Atlanta can determine risks for every laboratory in the country. And the government, as a result, also tells us how to mitigate those risks, by defining the laboratory type, such as BSL-2 or BSL-3, the PPE, the [safety] procedures, etc."

This top-down approach, he said, fosters a false sense of security: "Laboratories say, We don't need to think substantively about our unique risks, because the government has already told us what we need to do. That's a big problem."

Moreover, within the laboratory, biosafety and biosecurity have been "delegated very low down to an administrative officer with a checklist of requirements, but without the funding and authority to compel specific actions. They buy the PPE and make sure everyone has access cards, and then we check that box and move on . . . . We don't take the time to constantly ask ourselves, Is that the right PPE? Are those access cards working as intended?"

Although Salerno is quick to point out that the current system "has served us well historically," he would prefer to see "A, M and P in place in every single institution," to supplement national guidance. Generally speaking, he said, there is a need for greater intellectual sophistication in how laboratories approach their own safety and security, as well as greater leadership engagement in risk assessment and risk acceptance—since no laboratory can reduce all risks to zero.

Salerno calls for "a critical thinking process and documentation phase that is regular and repeatable and is repeated every time the situation changes, so, for example, new experiments, new materials, new equipment, new people, new information."

Changing Daily Behaviors

APHL's Biosafety and Biosecurity Committee is overseeing the association's work to support member laboratories as they refine their risk management systems and reach out to clinical laboratories in their jurisdictions. Pentella, who chairs the committee, said, "I think the biggest gap is that biosafety is not uniformly incorporated into the daily work behaviors of the nation. And that's what we need to have—education and training and leadership to make sure everyone is following best practices."

APHL's Biosafety and Biosecurity Committee is overseeing the association's work to support member laboratories as they refine their risk management systems and reach out to clinical laboratories in their jurisdictions. Pentella, who chairs the committee, said, "I think the biggest gap is that biosafety is not uniformly incorporated into the daily work behaviors of the nation. And that's what we need to have—education and training and leadership to make sure everyone is following best practices."

Ultimately, "people need to care about safety," said James Snyder, PhD, D(ABMM), FAAM, a member of the Biosafety and Biosecurity Committee and professor of pathology and laboratory medicine at the University of Louisville in Kentucky.

A brief survey Snyder conducted on the American Society for Microbiology ClinMicroNet last December (with eight clinical laboratory responders and two public health laboratory responders) provides anecdotal evidence that laboratory safety is indeed a work-in-progress.

One respondent, for example, reported that 40 technologists in his institution were tested for Brucella antibodies and three placed on prophylactic therapy after potential exposure to a culture at the open bench; the suspect organism was later identified as Hemophilus. Another respondent reported potential exposure to Neisseria meningitidis from respiratory specimens. And all respondents cited the need for additional biosafety measures in their laboratories, such as risk assessment training, enhanced containment systems and instruction in the recognition of unusual pathogens in patient specimens. Wrote one respondent, "I am still unsure about sending suspected [Ebola] specimens through our automated chemistry/hematology lines."

To address these gaps, the APHL Biosafety and Biosecurity Committee has begun several activities:

  • Development of training workshops and webinars, delivered either through APHL's Public Health Preparedness and Response Program or the APHL/CDC National Laboratory Training Network. In addition, APHL is co-sponsoring the Laboratory Safety Leadership Summit planned for February, and its members spoke at the 14th CDC International Symposium on Biosafety, which began in January.
  • Creation of online forums to foster a community of practice around biosafety and biosecurity.
  • Creation of an online repository of outreach models, training courses, risk assessment templates and other biosafety and biosecurity tools that can be applied to clinical laboratories.

Last year, the APHL members approved a position statement urging laboratories to enhance their biosafety practices via "routine risk assessments and standardized training, identification of true risk and best practices, development of consensus standards and guidelines, and improved reporting of exposure events."

The association is also promoting these measures abroad. Isatta Wurie, PhD, an APHL consultant in Sierra Leone, said Africa's laboratorians are accustomed to using PPE, but it "wasn't considered" for workers engaged in the pre-analytical phase of the testing process—specimen collection, processing and transport.

Said Wurie, "The discomfort of wearing full PPE in a warm climate is very different from wearing PPE in air conditioning. . . . . One of the greatest ways to have errors is to start sweating when you go around to collect [specimens]. When you are hot, and sweat is pouring out of you, there is a tendency to use your gloved hand to wipe your forehead or to take off your PPE rapidly because of the heat. It's a big challenge."

To minimize risks, she said, "the laboratory response team came up with a formula." Healthcare workers don PPE for no more than one continuous hour, allowing time for one person to collect up to six patient specimens.

That guideline translates into at least three workers for a 25-bed Ebola facility—a supervisor and two people who take turns going into the infection "red zone."

In addition, the military was recruited to transport specimens to testing laboratories, simultaneously supplying an extra measure of security and "authority to weave through traffic in a much shorter time, thereby being within the desired turn-around-time."

Wurie is assisting national officials as they finalize Sierra Leone's first standard operating procedures for outbreak response. "Inasmuch as it's a health issue," she said, "it's also a national security issue." For example, there has been no standard policy for the storage and disposal of Ebola specimens, which are currently distributed among a number of mobile and fixed laboratories operated by international responders. Wurie said, "A national team is working on an inter-country policy and specimen repository for all three [Ebola] affected countries [in West Africa]."

Finally, Sierra Leone will benefit from a multi-country APHL effort to certify the functionality of laboratory biosafety cabinets—another quality element that has been absent.

Engendering Trust

Yet, even with all the domestic and international work ongoing to bolster laboratory safety and security, important questions remain unanswered.

Said Pentella, "We had a lot of opinions [about Ebola biosafety] in 2014, but none of it is backed by research. One of the goals of our committee is to advocate for research in this area."

Similarly, Salerno noted, "A lot of the traditional mitigation measures that we use are good ideas, and may work well, but are not necessarily supported by scientific evidence. And there are a lot of risks we don't fully understand — how particular agents might be transmitted or how much a particular instrument, like a vortexer or centrifuge, might aerosolize an agent depending on how it's being used. Decontamination is another issue—Does the nature of the material you place in an autoclave affect its performance?"

Pentella said one of the most common safety questions he gets asked, especially by young professionals, is Do you wear gloves or do you not wear gloves when handling culture plates? A related concern is how to reduce the risk of contaminating the outside of culture plates when working in a biosafety cabinet.

The lack of a rigorous, applied biosafety research program, said Salerno, has meant that some safety solutions have been over-engineered. He said, "We spend a lot of money on engineered solutions to protect us from the unknown, instead of spending money on research to minimize the unknowns."

In his view, the persistence of so many unanswered questions is yet another reason to move safety and security out of laboratories' administrative offices and into their scientific offices: "My belief is, if we had a more intellectually vibrant risk management system in place, and scientists more engaged in the risk assessment process, then they would create and promote and argue for the research agenda."

Plus, said Salerno, over time, a good risk management system will improve laboratory effectiveness and "engender trust and confidence among the employees, customers and collaborators"—something that might well make a difference when the next scary pathogen comes to town.