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Since anthrax was sent through the U.S. mail in October 2001, the nation’s first responders have been using commercially available detection devices to test suspicious powders. The attacks inspired fear, panic, false alarms, and hoaxes – and some helpful change as well. There was a clear need for a structured process, with open lines of communication, reliable testing, and accurate results – all as quickly as the equipment would allow and the specific emergency situation demanded.
Progress has been made since 2001, when the U.S. General Services Administration (GSA) first developed guidelines for how to handle an anthrax threat. The massive annual increases in the budget requests for homeland security during the past several years make it clear that there has been no lack of financial support for such projects. And yet, nearly six years after the first known acts of biological terrorism on American soil, and after a national study was funded to determine standards for detection devices for Bacillus anthracis (anthrax), U.S. national policy and federal guidelines have yet to reflect the results of this progress. The Gold Standard
The CDC (Centers for Disease Control and Prevention) is considered the authority on disease prevention and control and has a validated lab test for anthrax determined to be the “gold standard” by the White House Office of Science and Technology Policy (OSTP). However, lab tests are not field tests and this poses a time problem. Assuming that samples from an exposed site arrive at a properly equipped lab in suitable testing form, results can be determined within 24 to 48 hours after the sample has arrived. The good news is CDC has partnered with the Laboratory Response Network (LRN) to form a network of certified labs able to perform tests andentify biological threats such as anthrax. As of the end of 2006 there were over 100 labs in the network. This is in addition to state health departments and public health labs that have the capacity to test for suspected biowarfare agents.
A positive test for anthrax at a lab level would be confirmed by testing done by the CDC itself. Some of this testing involves growing the organism to verify if it is live and virulent – testing that is of critical importance but can take several days. There is no doubt that these tests are necessary to confirm andentify the strain of anthrax, but they do not allow on-site decision making that can be critical to the people on the scene and for proper evidence handling to prosecute those responsible for release of the anthrax.There also are concerns about the safety of first responders entering a site possibly contaminated by a suspected biological agent. CDC made certain interim recommendations, in October 2001, for safety gear usage during a potential exposure to biological hazards. The CDC certified the self-contained breathing apparatus (SCBA) respirator, equipped with a full face piece, as providing the highest level of protection against airborne hazards. Half-mask or even full-face-mask air-purifying respirators with particulate filter efficiencies recommended for exposure to biological hazards such as pulmonary tuberculosis and the hantavirus are endorsed as the minimum level of protection for exposure to anthrax. Protective suits are also suggested. Hoaxes, Reliability, and the DOD Exception First responders took the CDC personal protective gear recommendations seriously – but they also took commercially available anthrax-detection devices with them. The reason was obvious: A quick verification test can save lives and thousands of dollars. If the devices do not detect anthrax, it means the responders probably are investigating a hoax. Unfortunately, the commercially available devices used were not always reliable. For that reason, and possibly others, a 2002 OSTP memorandum advised a freeze on ordering any anthrax testing equipment. The memo stated, among other things, that “recent scientific evaluation of these commercial available detection systems concludes that this equipment does not pass acceptable standards for effectiveness. … Field-testing solely using commercially available polymerase chain reaction [PCR] or handheld immunoassays [HHA] for the detection of Bacillus anthracis is not recommended.” The OSTP memo did not describe the evaluation process for PCRs and HHAs in detail, but did state that the detection thresholds set for the devices required a level of anthrax that was above the minimum level needed for infection. In other words, there could be enough anthrax at the site to infect humans, but not enough for the device to register a positive result. In addition to this problem, OSTP found that at least some of the devices were giving false positives.
Although calling for a termination of current and future federal orders of PCRs or HHAs, OSTP singled out the Department of Defense as an exception to the freeze, stating that DOD would be able to “continue to procure military-standard biological-detection equipment” under its own regulations. DOD has for some time used HHAs as a standard equipment item in its biological-warfare (BW) detection program, and after receipt of the OSTP memo issued a document, including a white paper on HHAs, to support the department’s continued use of such devices. “HHAs can be properly employed to provide information in an expedient fashion when they are used as intended and are supported by additional technologies,” wrote Dr. David Cullin in the DOD response. “HHAs were designed to provide data quickly,” he continued, “to enhance early command assessment and response to a given scenario.” DOD further pointed out that HHAs “provided the first indication of the presence of Bacillus anthracis in the letter sent to Senator Daschle” (the reference here is to an anthrax-laced letter received in late September 2001 in the offices of then-Senate Majority Leader Thomas A. Daschle (D-S.D.).
The issue at hand – the reliability of detection devices, specifically HHAs – was a legitimate concern. HHAs are extremely sensitive and, although DOD supported the use of HHAs, the department was careful to emphasize that the devices had to be properly used and should be supported by additional technology. By design, HHAs are not meant to be the only form ofentification for BW agents, and are not prescribed for diagnosis. They are designed to presumptivelyentify one BW agent; in the case of anthrax, the HHA is meant to answer one question: Is Bacillus anthracis present? There was no government-recognized test done of the HHAs to standardize the market at the time the OSTP memo was issued. So, although DOD supported the use of HHAs by first responders, there was no way to rule that one device was better than another or even if devices met minimum acceptable standards. Setting the Standards The Department of Homeland Security established its own Science and Technology (S&T) directorate in 2003 to conduct “research, development, test, evaluation, and timely transition of homeland-security capabilities to federal, state, and local government and private-sector entities to anticipate, prevent, respond to, and recover from terrorist acts.” The 2004 DHS budget for Science and Technology requested $25 million for a Standards Program both to focus on the development of test and evaluation criteria and to “conduct analyses for state/local first-responder detection equipment and communication protocols.” The DHS S&T Standards Portfolio partnered with OSTP and the Office of Management and Budget to form an interagency group to develop national standards for biological detectors. The S&T directorate also reached out to AOAC International, a scientific association committed to “worldwide confidence in analytical results,” to develop the standards. The AOAC created a task force that included DHS Director of Standards Bert Coursey, OSTP Assistant Director of Homeland Security Lawrence Kerr, and a broad spectrum of experts on anthrax, validation study design, and assay development from 36 federal and nine military agencies, complemented by representatives from numerous state agencies, academia, industry and first-responder units. This task force recommended inclusion and test criteria, and a study design for the standards test. For a device to be included in the AOAC testing the HHA had to be portable and able to provide results in less than 30 minutes; in addition, the test had to be reasonably easy to do and the test results easy to read. The HHAs also had to be beyond the research and development stage, and those that fit the AOAC criteria had to use a lateral-flow format – which means they test and present results in a fashion more or less similar to a pregnancy test. (More simply stated, the sample is applied on one end of the device, and after a certain amount of time, the results appear on the other end.) The AOAC used two recognized programs for validation of analytical methods, the Performance Tested Methods (PTM) and the Official Methods for the HHAs test data. Briefly stated, PTM calls for test kit performance evaluation, reproducibility testing, and stability data (which tests the shelf life of the kit). The Official Method includes test data review by a committee, and a collaborative study – i.e., a performance test in 10-12 labs to determine lab-to-lab reproducibility – followed by another round of data reviews. The AOAC synchronized the two methods for the first time when testing the HHAs. The PTM results became the first phase of the testing; the second phase was the collaborative study component of Official Methods. During this same time frame, AOAC scientific consultants met with CDC scientists to review the way that the Laboratory Response Network was confirming the initial anthrax test results. After much collaboration between the two groups, the LRN method for presumptiveentification of anthrax (the screening test) was approved as the Official Method for the standardization tests. Carrying Out the Tests Five HHAs were selected for testing. The first phase of the testing determined a device’s ability to detect anthrax, to distinguish Bacillus anthracis from non-Bacillus anthracis, and to measure the sensitivity of the device when a certain quantity of anthrax spores are present and when a certain quantity of non-Bacillus anthracis spores are present. This phase of the testing program was completed in one lab. The second phase of the testing involved 12 labs analyzing common samples to test the reproducibility of the HHA results. The two phases of the testing replicated the multiple lab process of the LRN and CDC. Completing the first phase of testing implied that the HHA can provide clear and reliable results; completing the second phase aligned the HHAs’ testing accuracy with the CDC’s process. In short, a positive anthrax result from an HHA that meets the AOAC’s standards should be as accurate as the LRN results. When phase one of the testing program was completed in November 2004, only one of the five HHAs tested passed the tests – Response Biomedical Corporation’s RAMP anthrax test, which met the reliability and sensitivity standards. AOAC Executive Director James Bradford summarized the results as follows: “Response Biomedical's RAMP was first approved by AOAC as an Official Method of Analysis (our certification) for laboratory use only.” After the final rounds of testing and data review, RAMP was certified, so the AOAC was able to approve it for field use, Bradford said. As of early April, RAMP was still the only HHA to be certified for field use for the detection of Anthrax by the AOAC. Reading the Results Bradford said that a second round of HHA testing is now underway. Meanwhile, although the CDC collaborated with AOAC on the validation methods, the CDC still does not recommend the use of HHAs. The agency’s policy toward HHAs has not changed, in fact, since the official health advisory issued on 18 October 2001. That advisory states that “These assays are intended only for the screening of environmental samples. First-responder and law-enforcement communities are using these as instant screening devices and should forward any positive samples to authorities for more sensitive and specialized confirmatory testing. The results of these assays should not be used to make decisions about patient management or prophylaxis.” The CDC is not the only federal agency wary, despite the AOAC testing, of recommending HHAs. The DHS policy toward HHAs is in line with the federal government’s overall policy, which remains the same since the 2002 release of the OSTP memo. “The federal government position as stated by Dr. Marburger at OSTP in July 2002 is that first responders are not to use HHAs,” according to one official statement. “DHS and other agencies continue to develop standards for both anthrax (Bacillus anthracis) and ricin so that first responders will understand when they could use these detectors for screening visible suspicious powders and the limitations of the technology. At this time, DHS does not recommend their use.” Any equipment that the DHS does recommend is included on both the Authorized Equipment List (AEL) and the Standardized Equipment List (SEL). A search of both lists reveals a listing for a field-assay kit for the detection of biological agents, but includes, in boldface type, the following notation: “Recommendations from IAB - NOT DHS requirement or part of DHS grant guidance.” IAB – the InterAgency Board for Equipment Standardization and Interoperability – was founded in 1998 by DOD and the Department of Justice. Its mission is to establish coordinating standards for first responders for preparing for or responding to chemical, biological, radiological, nuclear, or explosive incidents at the local, state, and federal levels of government. Policy, Practice, and Practical Considerations There is policy, and there is practice – and the two are not necessarily, and not always, the same. The nation’s first responders have been using commercially available detection devices for some time now, and will undoubtedly continue to do so. “One has to weigh public safety concerns with accuracy, and preservation of evidence,” says former fireman, first responder, and detection expert Christopher Hawley. “Not all HHAs are created equal, and some are better than others. With the AOAC testing, RAMP has been shown to be an accurate device for visible powder with accuracy rates in the 97-98 percent and higher range. Some HHAs have been shown to have 30 percent or less accuracy rates. Some HHAs have issues with false negatives – where real anthrax is present but the HHA doesn't see it, which is a large concern. “As a former local responder,” Hawley continued, “I am not in favor of the federal government recommending one particular technology over another. … There are many tools in the detection device toolbox, and HHAs are one tool.” Hawley is a highly qualified RAMP trainer, and has written books on detection and various related issues. He says that what is really needed is a highly accurate device that is also relatively inexpensive – but to get that, additional research and development is required. “There are a number of new technologies that are in the research phase that we are told look promising, but are still 5-10 years away from first responders.” The most important component of using an anthrax detection device is the knowledge factor. “When testing for biological threat agents, we have stepped