The Laboratory Response Network

The CDC's LRN was established in 1999 in compliance with a presidential directive that outlined federal agencies' countert-errorism goals and responsibilities. The mission of the LRN is "to maintain an integrated national and international network of laboratories that can respond quickly to acts of chemical or biological terrorism, emerging infectious diseases and other public health threats and emergencies.'' The LRN was first tasked to address state and local public health laboratory preparedness and response for bioterrorism. Since its inception, its mission has expanded to include chemical terrorism. The scope of laboratories in the LRN has expanded beyond state and local public health laboratories in order to meet national security needs (

The LRN and its partners maintain a network of laboratories that can respond quickly to acts of chemical or biological terrorism, emerging infectious diseases, or other public health threats and emergencies. The network included 152 federal, state, and local public health; military; and international laboratories as of August 1, 2005. Figure 8.1 shows the distribution of LRN laboratories by type as of March 11, 2005. The LRN employs tests that can detect biological threat agents in clinical specimens, environmental samples, food, animals, and water. The Association of Public Health Laboratories was a partner in the early development of the LRN and has played an important role in ensuring that the LRN provides the training, standardized methods, and equipment necessary for detecting biologic agents of terrorism and other threats to public health. The Federal Bureau of Investigation (FBI) was also a key partner in establishing the network. The FBI brought its forensic expertise and evidence-gathering requirements to the program. Public health and law enforcement have overlapping approaches to their investigations that required collaboration between CDC and law enforcement to both enhance and protect the integrity of their investigations.

Three levels of laboratories are recognized within the LRN for bioterrorism agent detection. LRN laboratories responsible

Laboratory Response Network

FIGURE 8.1 Map of Coverage of the Laboratory Response Network (LRN) in the United States, 2005.

Updated January 7.2005

FIGURE 8.1 Map of Coverage of the Laboratory Response Network (LRN) in the United States, 2005.

for bioterrorism agent detection are designated as national, reference, or sentinel laboratories (Figure 8.2). The national laboratories include laboratories at the CDC, USAMRIID, and the Naval Medical Research Center. They have unique resources to safely identify highly infectious agents (biological safety level 4 agents) and the ability to provide definitive characterization of biologic agents. The national laboratories have developed standard tests and protocols, trained laboratory analysts, and established secure communications for the rapid sharing of laboratory results from reference laboratories.

Reference laboratories in the LRN perform tests to detect and confirm the presence of biological threat agents, such as those that cause anthrax, plague, tularemia, smallpox, or botulism. These laboratories ensure that state and local laboratories can have a timely response in the event of a bioterrorism incident or an emerging disease. Rather than having to rely on confirmation testing from national laboratories, reference laboratories are capable of producing conclusive results needed by local authorities for rapidly responding to emergencies. Specimens received by reference laboratories that contain threat agents are usually submitted to a national laboratory for definitive characterizations of the agent. State and local public health laboratories comprise most of the reference laboratories within the LRN.

Although sentinel laboratories are not counted among the LRN laboratories, they represent the thousands of clinical (human and veterinary) and environmental laboratories identified by the state LRN reference laboratory to serve as the front line of defense in detecting agents of terrorism. Qualification of the sentinel laboratory is based on the experience and competency of the laboratory staff, appropriateness of facilities, and completion of training provided by the LRN. Sentinel laboratories can often rule out potential bioterrorism agents based on a battery of simple tests. In a covert terrorist attack, a sentinel laboratory could be the first facility to identify a suspicious agent or an unusual cluster

FIGURE 8.2 Laboratory Response Network (LRN) structure for bioter-rorism response laboratories.

of diseases. A sentinel laboratory's responsibility is to rule out other diseases and refer a suspicious sample to an appropriate reference laboratory.

The LRN uses an array of presumptive and confirmatory assays to detect biological threat agents or chemical agents. Presumptive assays generally include traditional microbiological assays, such as growth on special media, use of special stains, and the use of rapid molecular diagnostic assays, such as real-time PCR. Confirmatory methods used by the national laboratories are considered the gold standard for detecting the target agent. Methods, such as time-resolved fluorescence (TRF) and molecular characterization, have replaced many of the more traditional confirmatory methods that were based on the growth and biochemical properties of the agent. Reference laboratories have access to LRN protocols through a secure Web site and are supplied standardized reagents needed to perform the necessary tests. Uniform procedures for use by sentinel laboratories have also been developed and are used for training of sentinel laboratory staff. All laboratories that are part of the LRN must provide a safe and secure environment for performing tests and must participate in a recognized proficiency testing program.

The chemical component of the LRN employs a more centralized structure, with only a few laboratories currently prepared to provide definitive analysis of specimens for chemical agents or their metabolites. LRN laboratories responsible for chemical agent detection are designated as level 1, 2, or 3 laboratories. Five laboratories located in California, Michigan, New Mexico, New York, and Virginia participate in level 1 activities. At this level, personnel are trained to detect exposure to an expanded number of chemicals in human blood or urine, including all level 2 laboratory analyses, plus analyses for mustard agents, nerve agents, and other toxic chemicals. Forty-one laboratories participate in the chemical LRN by providing level 2 activities. At this level, laboratory personnel are trained to detect exposure to a limited number of toxic chemical agents in human blood or urine. Analysis of cyanide and toxic metals in human samples are examples of level 2 laboratory activities. Each of the 62 chemical network members participates in level 3 activities. Level 3 laboratories are responsible for the following:

• Working with hospitals in their jurisdiction

• Knowing how to properly collect and ship clinical specimens

• Ensuring that specimens used as evidence in a criminal investigation are handled properly and chain-of-custody procedures are followed

• Being familiar with chemical agents and their health effects

• Training on anticipated clinical sample flow and shipping regulations

• Working to develop a coordinated response plan for their respective state and jurisdiction

Initial testing in a suspected chemical event will occur at CDC or 1 of 5 level 1 chemical laboratories that have been established by CDC. By use of mass spectrometry, CDC laboratories perform tests on the first 40 or more clinical specimens to measure human exposure. Results of these tests would be reported to affected states, and if needed, appropriate LRN members may be asked to test additional samples. This approach is necessary because the analytical expertise and technology resources required to respond to a chemical event is expected to be high.

The LRN supports secure communications on emerging and emergency issues, a secure mechanism for ordering reagents and testing protocols, and a system for electronically reporting test results. The LRN provided valuable testing after the release of anthrax spores in 2001, the identification of monkey pox in 2002, and the response to severe acute respiratory syndrome (SARS) in 2003.

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