Nation's labs rising to biological threat, still lag on chemical agents

Surge capacity improved since anthrax madness

The nation's laboratory capacity and ability to detect biological agents has increased dramatically in recent years, but continues to play "catch up" on chemical and radiological preparedness. While something of a work in progress, the Laboratory Response Network (LRN) is the key to rapid identification and response should terrorists strike with either biological, chemical, or radiological weapons.

"Both the chemical and bio sides of the LRN are designed so that positive results from rapid test procedures are able to initiate a public health response," says Mike Miller, MD, PhD, chief of the laboratory response branch at the Centers for Disease Control and Prevention. "They are actionable. If you get a positive, somebody needs to do something quickly."

However, upgrading laboratory capability and capacity to detect chemical agents remains problematic. While Congress has provided funding to support the surveillance and control of infectious bioterrorism agents since the early 1990s, federal funding for laboratory response to chemical terrorism has only been available since 2003. As a result, laboratory preparedness for chemical terrorism trails considerably in comparison to bioterrorism preparedness, the Association of Public Health Laboratories (APHL) reports.1

While problems remain, chemical lab resources are incrementally increasing. The LRN currently has 62 state, territorial, and metropolitan public health laboratories that are members of its chemical component. "Within the LRN, there is extensive and elaborate testing capacity for chemical agents — nerve agents, all types of chemicals, blisters agents, etc.," Miller says. "I think right now some of the core labs, the main labs certainly at CDC and at four other sites around the country can detect about 150 different chemical agents."

Progress in the biological response area has come at no small price. Laboratorians and hospital clinicians alike ruefully recall those maddening months in 2001, when the still-unsolved anthrax mailings set off a wave of hoaxes and false powders. Given the tenor of the times, everything had to be taken seriously and just about everything was. Never have so many lab workers spent so much time and energy to identify a panoply of powders including baking, talcum, salt, and other benign substances. Geared to respond to human specimens, the LRN was nearly swamped under the tsunami of environmental samples. "A small group of public health laboratory leaders literally worked around the clock to devise a standard protocol to test such items," the APHL reports.2

But through that trial by fire, the nation's laboratory system has come out stronger than ever. There now are 150 biological LRN reference labs, with at least one in every state. In 2001, there were only 91 participating labs. The LRN is now completely interlinked to handle surge capacity, Miller explains.

"We are miles ahead of where we where," he tells Bioterrorism Watch. "Every laboratory in each state may — because of its size — have a different overall capacity, but by being a member of the LRN they work under a single integrated operational plan. The states have agreements with each other and other laboratories so that during a surge [threat] or a real event other labs could help them with their testing. That was clearly illustrated during Katrina, when New Orleans had to use that plan. The specimens that would normally have gone to laboratories in New Orleans were [routed] to other labs that had agreements with them. That occurred within hours of a phone call."

Rapid molecular testing is now standard in many labs, meaning the ability to identify the Category A and B bioterrorism threat agents has increased significantly. "The molecular testing platforms that we have developed have been distributed throughout the LRN," he says. "They are capable of detecting virtually any of the agents of bioterrorism and [many] chemicals."

For example, the number of labs able to identify three key bioterrorism agents increased from 2004 to 2005 as follows: anthrax from 84 labs to 95 labs; ricin, 51 labs to 71 labs, and plague, 83 labs to 93 labs. "Every state in the United States [now] has at least one LRN laboratory," Miller says.

BSL labs increasing as H5N1 looms

The number of Bio-Safety Level 3 Labs — which are needed to work with avian influenza A (H5N1) and other high level infectious agents — has increased to 139. Only 69 BSL 3 labs were in operation in 2001. "Those are critical in terms of safety to the laboratorians that have to manipulate those organisms," he says. "By being able to work in a BSL 3 lab, there are safety measures that are in place to protect the workers from risk of getting infection because of accidents. It reduces the risk of accidents very significantly."

Still, the APHL reports that 36 of 51 labs (71%) responding to a recently published survey said they did not have a BSL-3-enhanced laboratory and therefore cannot culture the avian influenza A virus (H5N1). "These [labs] are allowed only to screen specimens for the presence of the virus using the real-time reverse transcriptase PCR assay provided by CDC," the APHL found. "Testing of samples where live virus confirmation is required will need to be referred to CDC or other federal or agricultural laboratories, which may delay confirmation."

Similarly, strides have been made in the ability to detect smallpox virus, but blind spots remain in the system. The APHL survey found that 49 of 51 (96%) responding labs have validated polymerase chain reaction (PCR) and direct fluorescent assays for the detection of varicella zoster virus, the causative agent for chicken pox, the disease most likely to be confused with smallpox. However, only 22 of 51 labs (43%) have a validated PCR assay for smallpox, though 20 others expressed an interest in developing smallpox-specific testing capability. "Due to the strict criteria for biocontainment of the smallpox virus, CDC continues to evaluate the feasibility of expanding smallpox testing capability," the APHL reported.

On a positive note, the APHL survey found ample evidence of ongoing lab upgrades in specimen and mail receiving areas, air handling systems, HEPA filtration systems, redundant fan systems, dedicated power/generator systems, biohazard disposal processes, subzero freezer capacity and reagent storage facilities. However, concerning the latter, the LRN is struggling to maintain testing supplies and reagents needed to identify specimens.

"State and local LRN reference laboratories typically respond to bioterrorism threats and hoaxes several times a week," the APHL reported. "To meet these ongoing public health and law enforcement testing needs and assure adequate capacity to respond to an actual outbreak situation, [labs] must continually replenish stores of testing supplies and standardized LRN reagents."

Early this year, APHL released data from a current assessment of LRN laboratory reagent needs showing that 51 of 83 state and local LRN reference laboratories (61%) have experienced delays receiving CDC-supplied LRN reagents for detection of potential agents of biological terrorism.

References

  1. Association of Public Health Laboratories. Ready, Set, Respond: Chemical Terrorism Preparedness in the Nation's State Public Health Laboratories. March 2006. On the web at https://www.aphl.org/docs/chem_t_final.pdf.
  2. Association of Public Health Laboratories. Public Health Laboratory Issues in Brief: Bioterrorism Capacity. May 2006. On the web at https://www.aphl.org/docs/2006_bioterrorism_capacity_final.pdf.