Other Ways To Find The Bugs

It is not necessary to physically capture and identify a given biological agent in order to determine its presence in a population. Other indicators are available that can provide the initial observation of an agent’s presence or provide information that can be used in conjunction with sensor data to confirm an agent. Following is a brief description of data sources in varying stages of development that could be used in an integrated, broad, biosecurity reporting system.

Prodromic Data

Prodromic data is information gained prior to the recognition of disease symptoms in organisms. An example of such surveillance may be the monitoring of immunological markers found in the blood of an organism that does not yet display any symptoms of illness. 24 These markers are some of the earliest indicators, appearing almost instantaneously when the body’s defenses are activated. Advances in immunology, molecular biology, and genetics have opened new possibilities for recognizing biological markers to diagnose a range of illnesses, from diabetes 25 to cancer, 26 before symptoms are noticeable.

Much of the work being done in prodromic data collection is still experimental and being carried out in various immunology laboratories around the country. The task of finding specific indicators is a challenge, because the innate human immune response is, for good reason, a rather generic one. (See figure 15 for a simplified view of how the immune system works.) The body is exposed to thousands of harmful triggers called antigens and must be able to respond to each effectively. For our benefit, the immune system cells produce an adaptive immune response that creates long-term, antigen-specific proteins called antibodies. 27 These basic components of an immune response are very likely not the only response the body produces when exposed to disease agents. Researchers at the National Institute of Allergies and Infectious Diseases (NIAID) believe that a number of potential markers exist and have begun organized efforts to effectively evaluate their utility. 28

Figure 15 – Schematic view of human immune system. Some researchers suggest monitoring early immune response as a way of detecting bioattacks. Source: NYC Comprehensive Health Curriculum.

Another intriguing application of prodromic surveillance involves the development of a rapid, sensitive, and reliable method to diagnose respiratory infections to rapidly distinguish between infected and non-infected persons. 29 Researchers are developing new, rapid techniques to analyze proteins in the breath of persons with respiratory infections, such as inhalation anthrax. The new techniques take seconds to minutes to accomplish, compared to current laboratory assays that take hours to perform. 30 The current research focus in this area is to define the proteins in exhaled air and in body fluids, such as saliva and urine. Researchers also are examining the immune responses that occur in the lung in response to exposure to biological agents. Rapid diagnosis using breath analysis would be a vital capability during a biological warfare attack, because hospital emergency rooms could be overwhelmed by the “worried well.” Also complicating diagnosis is the fact that initial symptoms for a biological agent infection are generally indistinguishable from symptoms for a common cold or flu. Early and immediate treatment of infected persons would improve their prognosis for recovery.

Syndromic Surveillance

Syndromic surveillance refers to the observation of signs or symptoms that characterize an abnormality, such as a disease outbreak in a population. This is a broad designation of the term meant to include observations by medical professionals and the public health sector, as well as from pharmaceutical sales, medical claims reporting, and veterinary surveillance. All can provide valuable information for biological detection. The goal of syndromic surveillance is essentially to shorten the delay between the appearance of the first cases and intervention. 31 This would minimize person-to-person transmission and provide for timely treatment. The value of syndromic surveillance was evident in the postal anthrax attacks in 2001. During the incident, the patients who survived were those who were diagnosed and treated early. 32 In fact, six of eleven patients with acute inhalation anthrax survived because they were diagnosed early and received immediate treatment with antibiotics. The early diagnosis and quick response of public health professionals prevented a much greater tragedy.

Health care professionals gather and record valuable information that could be crucial in detecting an attack, if it were quickly monitored and interpreted. Hospital facilities use computer systems to compile data from departments throughout their organization. This includes registration and billing information, clinical observations, emergency room management, radiology, laboratory, and pharmacy services. Since the amount of information recorded is significantly large, computer programs are typically used to maintain organization and accessibility for personnel. Electronic medical records systems are an example of such programs. If these programs were easily accessible for public health monitoring, they would be valuable tools for disease and bioterrorism surveillance.

Unfortunately, comprehensive medical records systems are not widely implemented in hospitals nationwide and are even less frequently used in physicians’ offices. 33 In hospitals that do use computer databases, the information is rarely linked or shared with other hospital record systems.

Local and state health departments gather information directly through their own investigations as well as from healthcare professionals. In fact, epidemiologists have been systematically collecting data about disease outbreaks for decades. Currently, the Federal Government uses a few systems for recording a core set of data. Fifty states, the District of Columbia, New York City, and five U.S. territories all gather information via the National Electronic Telecommunications Surveillance System (NETSS) and transmit it to the Centers for Disease Control. 34 There are other disease surveillance systems that collect reports on single diseases, such as the National Malaria Surveillance System. Unfortunately, while the content of the information has great potential, and is a valuable aspect of confirmation, the overall capability of these systems for real-time biological detection is rather low.

Both medical and public health surveillance are considered to be rather slow indicators of a biological attack. It was mentioned above that a CDC study showed these sectors as being a promising source of biological detection. While the proportion of outbreaks reported was high, the length of time between the first reported case and the identification of the problem sometimes exceeded a week or even two weeks. 35 Much of this time lag is a result of the poor system of communication between healthcare enterprises and public health monitors. There are few direct links between hospital clinical information systems and the public health sector. The current method of data transfer is usually as follows: frontline healthcare professionals identify a reportable case, for which they fill out paper-based data collection forms that are sent to the local health department. From the local department, the data are either copied and filed to the state or transmitted through a computerized electronic data management system. Finally, at the state level, the data are manually entered into an electronic system. 36 Thus, the data become electronically available days to weeks later in a rather unorganized format, because there are no standard methods for public health reporting.

In December 2003, the Institute of Medicine (part of the National Academy of Sciences) called for hospitals and physicians to adopt electronic record-keeping systems that could form the basis for a nationwide network of patient information. 37 The Institute stated that the government would set the standards but would not direct what software clinics and hospitals should buy. Although requirements for participation in a national information network would not be mandatory, involvement would eventually become a prerequisite for participating in such programs as Medicare. A nationwide network would allow constant disease surveillance, which would be valuable in detecting and responding to bioterrorism incidents.

New public health surveillance systems are being designed to minimize this lag by improving and integrating electronic disease surveillance systems. One project now being implemented by the CDC is the National Electronic Disease Surveillance System (NEDSS). This network is a collaborative effort between CDC and state health departments to create an integrated and standardized electronic information system for communicable diseases. 38 The system would attempt to ease the burden on health care providers with standardized data collection and would enable earlier recognition of a problem through automatic electronic case reports to the state level. 39

Another system that is in compliance with NEDSS is Real-time Outbreak Disease Surveillance (RODS). The RODS project is a collaboration of health departments, hospitals and medical centers, foundations, and industries throughout Pennsylvania and northwestern Utah. 40 It is currently in operation and receives real-time data from emergency departments in these regions to be examined for incidents that are suggestive of disease outbreaks.

Computer surveillance systems such as these can report symptoms from emergency rooms or clinics that characterize a possible biological attack. However, it is difficult to choose which symptoms should cause alarm, since many illnesses show similar signs. For instance, anthrax cases often report a fever, chest pains, fatigue, cough, and an abnormal chest x-ray. Yet, the same symptoms are often recorded in flu cases and many viral and bacterial respiratory infections. If these symptoms were allowed to signal possible anthrax cases, confirmatory labs would be overwhelmed.

Complementary to the speed of reporting is accuracy of the information. The certainty of any indicator is vital, since false positive or negative results can be extremely costly both to human health and the economy. When using healthcare data for syndromic surveillance, one may be able to lessen the occurrence of false positives by considering a threshold level for detection that accounts for annual events, such as flu and allergy season. On the other hand, an outbreak such as SARS may initially go almost completely unnoticed if the rise in flu-like symptoms coincides with the number of expected flu cases during flu-season. 41

A similar problem arises if the spread of the outbreak occurs slowly. A simulation done by RAND Statistics Group showed very positive results for early detection in the event of a “fast outbreak,” that is, 18 reported cases in three days. However, when the same number of cases was reported over 9 days, the probability of early detection dropped significantly. 42

The location of the original reporting can provide another confounding variable for syndromic data from the healthcare field. False positives could appear in regions where certain diseases are endemic. For instance, higher incidence rates for cholera and plague were noted in the western United States and for tularemia in the central United States.43 Research done by the CDC describes disease-specific trends in demographic characteristics as well as geographic and seasonal distribution of conditions caused by certain biologic agents. Studies such as that done by the CDC, which identify patterns of endemic disease associated with these agents, establish a baseline against which future disease incidence can be compared.44 As a result, identifying the incidence of unusual diseases would become an easier and more reliable method of surveillance.

In summary, medical and public health surveillance systems contain a large array of information of potential value for early biological detection through syndromic surveillance. Most of this information is simply not collected, transferred, or made available through a means that would create the timely recognition of a problem. New programs, such as NEDSS, may be the answer to this problem. The improvements made for developing an effective syndromic surveillance system would create a stronger public health system as well.

Pharmaceutical Sales

The pharmaceutical sales industry is another possible informant for syndromic surveillance. Existing data bases used for market surveillance may be of use for biological detection. One such system is used for the management of prescription drug benefits plans. Pharmacies use online systems to verify health-care coverage for prescription plans and to assign the prescription to the appropriate supplier. 45 The information recorded includes the name and dosage of the drug, age and geographic information of the patient, and, in some cases, a code for diagnosis. The data enters a transactional system usually on a weekly basis and is uploaded to a data warehouse that can be made easily accessible to public health authorities. The system has the potential to define trends in prescription drug activity that could indicate a threat to public health. 46 However, cost and privacy issues could make access to these data difficult.

In addition to prescription drug sales, there may be value in monitoring over-the-counter (OTC) drug sales in detection of outbreaks or possible terrorist attacks. The data may be important as an indirect indicator of illness, if it can signal an outbreak before emergency rooms, health clinics, or even prescription drug surveillance. In theory, this could occur if persons with symptoms of illness buy OTC medications first, rather than rush to the ER or consult their physicians. Records of these sales could then be pooled and a detection algorithm used to identify irregular patterns of purchases. 47 For instance, a surge in the sales of a decongestant or cough medication could indicate an increase in bacterial infections or diseases with flu-like symptoms.

Figure 16 – Over-the-counter (OTC) sales can be monitored as one indicator of a possible bioattack. Source: Honolulu Advertiser, March 9, 2002.

Although OTC medication tracking will not facilitate real-time biodetection, monitoring OTC sales may be a piece of evidence for detection. Unlike medical surveillance, OTC sales are not symptom specific. For instance, an attack from a bacterial agent such as anthrax or plague could not be inferred directly from an increase in sales of items, such as Tylenol or Advil, each of which could be used for a variety of symptoms. Perhaps a general sense of the type of illness occurring could be gathered by inferring from a variety of drug sales, such as a combination of cough medicine with decongestant. However, there is little background data indicating the ways in which epidemics manifest themselves in OTC data. Thus, patterns and correlations of these sales and their usefulness for disease surveillance remain uncertain.

One French study did analyze a number of surveillance mechanisms for Influenza A, including OTC sales. They found OTC sales did indeed show a rise during epidemic weeks, but in comparison to other methods, such as emergency rooms visits, the data were less immediate and accurate. 48 Explanations for the delayed signal include the possibility that the majority of the public keeps enough OTC drugs in their homes that they do not need to buy more when symptoms occur. As a result, any rise in sales may indicate these persons are restocking rather than purchasing OTC drugs for their initial symptoms. Furthermore, there are a number of issues that may prove the data to be unreliable or difficult to use. For instance, initially the data recorded contains complete details of the sale, including the exact date and time, customer information, detailed information on each product, prices, etc. Not only is this dataset extremely large, but stores may be unwilling to release such information. 49 Also, sales of certain drugs vary a great deal seasonally, as well as according to pricing policies or on holidays. All of these factors could lead to inaccurate conclusions from the data.

Medical Claims Data Surveillance

Another source for syndromic surveillance data could be medical claims and billing information for detecting public health threats. Claims data are very comprehensive. They include demographic information, such as name, age, gender, address, ethnicity, and dependents as well as the patients’ complaint, physicians’ notes, and tests from laboratories and other medical procedures. The thoroughness of this resource makes it a possible tool for monitoring, detection, and aftermath analysis. However, the submission of information is rarely timely enough for early detection of a biological attack. Medical claims are submitted both on paper and electronically when an insured patient seeks medical attention. They initially enter a transactional system and accumulate until they are sent to a central data warehouse. It is from this warehouse that public health officials could access sufficient claims data that may indicate a possible outbreak. Unfortunately, as 30 days pass between the time the claim is filed and when the information becomes available from the warehouse. 50

Greater access to claims data could be improved through web-based and other electronic filing procedures for healthcare providers. These features are already becoming a ubiquitous feature of hospital and physician offices in the United States. If this source were pursued, however, the issue of client privacy would have to be addressed. This would likely result in a fee for access to the warehouse and an agreement relieving the warehouse operator of any liability. The cost of providing access to one data warehouse could reach millions of dollars and become even more expensive if used for day-to-day monitoring. 51

Sentinel Organisms – Animals as Collectors

In the search for the best method to warn of a biological attack, many scientists believe that nature may hold the answer. They argue that biological organisms may actually be more convenient and accurate monitors than machines. 52 Insects could pick up trace amounts of agents in the air or on the ground, acting as collectors. Insects performing this function are referred to as Key Insect Carrier Species (KICS). 53 The insects, which appear to be unaffected by the pathogens, are, in turn, collected with devices such as sticky papers and black lights and taken to a lab and tested for hazardous agents. There are at least two significant uses for KICS. First, they could serve for general monitoring of harmful biological agents. Second, they could have a specific detection application if released into a suspected BW storage or production site and recaptured to be examined. One researcher refers to insects used in that fashion as “flying crawling, Q-tips.” The advantages of using KICS are that they are a readily available and inexpensive source for collection and monitoring. Having the insects collect bioagents and then collecting them is only part of the process, though. Laboratory analysis of the insects for biological residues, just as with mechanical biocollectors, can be labor intensive and expensive.

Figure 17 – Key Insect Carrier Species—KICS—are proposed as a way to sample for the presence of biological agents. Source: http://www.rdc.ab.ca/rdc/organic_chemistry/biology/don_wales/insects/images/cockroach.jpg.

Sentinel Organisms – Plants and Animals as Collectors

Sentinel plants and animals are another alternative to ‘black box’ detection. Scientists at Penn State University and Colorado State University have been sponsored by the Defense Advanced Research Project Agency (DARPA) to genetically engineer plants that quickly change color if they come into contact with biological or chemical agents. 54 Because plants are stationary organisms, they have evolved to be highly sensitive to their environments. Even the simple flowering plant used in their research, Arabidopsis, a small weed in the mustard family, is estimated to have nearly 600 receptors and consequent response pathways.55 Through advanced bioengineering, these plants could be designed to perceive a biological or chemical input and respond in a predetermined way, such as producing a fluorescent protein causing them to glow.

There are numerous valuable benefits of this research beyond biological detection. If successful, it may also be used for naturally occurring disease and toxin surveillance or pollution monitoring. One aspect of concern, and an issue still not addressed, is the necessity for recharge capability, i.e., the plants would have to be designed to recover quickly to detect subsequent attacks.

The number of smell receptors in a human’s nose ranges from 5 million to 15 million, whereas in a dog, it can range from 125 million to 250 million. 56 In addition to more smell receptors, the olfactory portion of a dog’s brain is four times larger than a human’s. 57 The military is capitalizing on dogs’ abilities and training them to detect biological agents. In addition, it has also been noted that patients with smallpox and other biological agent diseases have a specific odor that could, theoretically, be detected by canines. 58

A very recent application of sentinel animals for biological agent detection occurred during the Iraq War of early 2003. Although the U.S. Marines brought state-of-the-art equipment to warn of a possible chemical or biological attack, their first hint of danger may have come from a pigeon. Because pigeons are more sensitive than humans to some biological and chemical agents, dozens of birds were distributed to Marine regiments in Kuwait to warn the troops of a chemical or biological release. 59 Just as canaries once warned miners of the threat of explosive gas, the U.S. military thinks pigeons may once again prove to be the difference between life and death. One sergeant commented that, "I got sensors that cost $12,000 and birds that cost $60 each and I place just as much trust in the bird as the sensor. Anything mechanical can fail or give us wrong readings." 60 Pigeons are good sentinels, because a lethal dose for them will not kill humans. The birds are also capable of detecting toxic gases if an industrial facility or water treatment plant were attacked. 61

Figure 18 – During the invasion of Iraq, some military units kept pigeons as sentinel animals to warn of the presence of toxic agents. Source: Associated Press Photo.

Another approach to using animals as an early warning and detection system is being explored by researchers at the University of Wisconsin-Milwaukee (UWM). The UWM Center for Water Security has received a one million dollar federal grant from the Department of Defense to create fish that glow when exposed to toxic agents. The Center’s goal is to help water utilities react to possible threats from biological or chemical pathogens. Scientists at the UWM institute are inserting a gene from the firefly into zebrafish. By linking the firefly gene to the zebrafish’s DNA, the fish emits a glow when toxic chemicals are present. 62

Cellular Sentinels

Another approach to using organisms as detectors is at the cellular level, using animal cells or single-celled organisms as indicators for the presence of a chemical or biological agent. The majority of this research has focused on ways to get cells to luminesce when exposed to a toxic agent.

Massachusetts Institute of Technology researchers have engineered mouse immune cells (white blood cells) to glow in response to biological agents.63 These special cells contain a jellyfish gene for a luminescent protein, as well as antibodies that respond to bacteria and viruses. When the antibodies on the sensor cells detect a pathogen, such as plague or anthrax, a surge of calcium is released. The calcium immediately activates the bioluminescent protein, causing the cell to glow.64 The cell system, developed with funding from the Defense Advanced Research Projects Agency (DARPA), has been successfully tested against many of the potential bioterrorist diseases such as anthrax, smallpox, plague, tularemia, and encephalitis. 65

Using this glowing cell system, first responders could test suspicious substances in subways, mailrooms, and airports. The cells would be a valuable tool, because they respond in 30 seconds to 3 minutes, compared to 30 minutes to several hours with current laboratory analysis. 66 Another valuable application of this system is as a diagnostic tool for doctors. Physicians could immediately identify patients with a disease of concern, such as Severe Acute Respiratory Syndrome (SARS), or those just infected with a cold. 67

A similar technique is being investigated at Virginia Polytechnic Institute and State University, where researchers are developing a lab-on-a-chip sensor that will detect trace amounts of toxins in water. 68 The sensor is composed of microscopic channels of fluid with E. coli bacteria, which release potassium when they come in contact with certain toxic chemicals. The potassium triggers a downstream photosensor to fluoresce as an indicator for a poison (biological or chemical) in the water. Such a sensor would be especially valuable as an early warning system to signal the requirement for additional analysis.69

Another approach to water biodetection is being done by scientists at Oak Ridge National Laboratory. The research plays on natural fluorescence in algae living in lakes, rivers, and reservoirs that are primary sources for drinking water.70 One key advantage in using these algae as biosensors is that they are naturally present in the water. This approach measures characteristics of fluorescence during photosynthesis, which changes when the algae is exposed to toxins in the water. The fluorescence induction data can be used as a real-time tool to detect toxic agents, making this system a significant method for around-the-clock monitoring, early warning, and field-deployable analysis. 71

Veterinary Surveillance

It is important to recognize that human health may not be the only target for a biological attack. Attacks on animal populations as well as agriculture are not only feasible, but have occurred. In 1915 and 1916 in Maryland, Virginia, and New York, horses and mules were the targets of biological warfare using Glanders and anthrax manufactured in Germany. 72 Additionally, there is compelling evidence that Rhodesian security forces infected cattle with anthrax in 1978-1980, during the Zimbabwe War for Independence, and that the Soviet military used Glanders against horses in Afghanistan in 1982 and 1984. 73 Whether targeted directly or indirectly, animal health is an important potential indicator of a biological attack. Consequently, another interest is the role of veterinarians in the detection of such events.

The veterinary profession is founded on service to society through both the protection of animal health and the promotion of human well-being. Their knowledge makes them well suited for the detection of biological weapons, because most recognized bioterrorist agents are zoonotic—that is, they cause diseases in animals that can be transmitted to humans. Such agents include plague, tularemia, anthrax, botulism, and hemorrhagic fevers, the majority of which are already familiar to veterinarians. Many biological pathogens produce similar symptoms in animals and humans. Because veterinarians are uniquely trained to observe such illnesses, most state governments maintain a position in public health specifically for a veterinarian. 74 Not only are veterinarians themselves familiar with diagnosing agents such as anthrax and plague, but veterinary labs also are well-versed in the diagnostics tests for these diseases and would likely prove useful in the event of an outbreak.

Currently, the ability of pets to act as sentinels is the focus of a number of veterinarians at Purdue University, where they are working on software for a national pet health surveillance database. These researchers have recognized that veterinarians may be the first to find symptoms of an outbreak, particularly if an animal population density is high in the affected area or if pets, due to their small size, are more susceptible than humans to agents that may have been released.

Additionally, information that might indicate an outbreak may be collected more promptly by veterinary surveillance than through public health surveillance. This is because of the existence of a centralized, standardized, veterinary hospital network system known as Banfield Veterinary Hospitals. The chain has 310 hospitals in 43 states, and Banfield’s vets see an estimated 1 to 2 percent of the nation's cats and dogs—about 2.5 million a year.75 The chain's hospitals and clinics use the same computer programs and data systems, in which data are entered weekly to a central computer. Such a system is far more effective for identifying a possible anomaly than the unlinked arrangement of physicians and hospitals used for human health surveillance. Veterinarians monitoring captive animals have already served as early indicators of an infectious outbreak: a veterinary pathologist at the Bronx Zoo gave the first alarm for the West Nile virus outbreak in the fall of 1999. 76

Figure 19 – Cats and dogs can be the earliest indicators of a biological attack, and veterinarians will need to play an active role in identifying and communicating potential threats . Source: http://www.hc-sc.gc.ca/vetdrugs-medsvet/approval_e.html.

24. Farzad Mostashari, Adam Karpati, “Towards a theoretical (and practical) framework for prodromic surveillance.” International Conference on Emerging Infectious Diseases, Atlanta. March 24–27, 2002.
25. Daniel E. Casey, et al., “Optimizing Treatment for Patients with Schizophrenia: Targeting Positive Outcomes,” The Center for Health Care Education, 2003. See <http://www.medscape.com/viewprogram/2589_pnt>, accessed February 2004.
26. University of Maryland Medical System website, “What Tests Indicate the Extent of Existing Prostate Cancer,” 2001. See <http://www.umm.edu/patiented/articles/what_tests_indicate_extent_of_existing_prostate_cancer_000033_8.htm>, accessed February 2004.
27. Neil A. Campbell and Jane B. Reece, Biology. 6th edition. (San Francisco, CA: Benjamin Cummings, 2002), 904-905.
28. “CombiMatrix Announces Commercial Launch of CustomArray, a Fully Customizable DNA Array Platform,” Business Wire, BioExchange, November 6, 2003. See <http://www.bioexchange.com/news/news_page.cfm?id=18816>, accessed March 2004.
29. http://www.darpa.mil/dso/thrust/biosci/ADVDIAG/Programs/scranton_jhu.html
30. Johns Hopkins University Applied Physics Laboratory homepage http://www.jhuapl.edu/programs/rtdc/Pathogens/RapidDetectionAndId.html
31. Stacy Hall, seminar remarks at the National Syndromic Surveillance Conference held by the New York Academy of Medicine, September 24 2002, access at <http://www.nyam.org/events/syndromicconference/2002/presentationpdf/stacy_hall.pdf>.
32. Ibid., 10.
33. Hall, 3.
34. Ibid., 3.
35. Hall, 12.
36. Centers for Disease Control and Prevention. “Supporting Public Health Surveillance,” accessed at <http://www.cdc.gov/nedss/>.
37. Doctors Advised to Keep Records Electronically” BizReport.com; November 21, 2003; <http://www.bizreport.com/article.php?art_id=5601>.
38. Patient Safety: Achieving a New Standard for Care; Philip Aspden, Janet M. Corrigan, Julie Wolcott, Shari M. Erickson, Editors, Committee on Data Standards for Patient Safety; Nov 20, 2003, 18.
39. Ibid.,18.
40. RODS Homepage, access at <http://www.health.pitt.edu/rods/>
41. Mike Stoto, RAND, seminar remarks at the Conference on Statistical Issues in Counterterrorism held at the Keck Center of the National Academies, 29 May 2003.
42. Stoto, 18.
43. Chang M, Glynn MK, Groseclose SL, “Endemic, notifiable bioterrorism-related diseases, United States, 1992-1999,” Emerging Infectious Diseases, 2003 May, accessed at <http://www.cdc.gov/ncidod/EID/vol9no5/02-0477.htm>.
44. Ibid., 25.
45. Ibid., 3.
46. Chang, et al., 3.
47. Goldenberg A, Shmueli G, Caruana R, “Using grocery store data for the detection of
bioterrorist attacks”, CALD technical report, Carnegie Mellon University, Oct. 2001., access at <http://www-2.cs.cmu.edu/~anya/papers/biodetectionStatMed.pdf>.
48. Philip Quenel, William Dab, Claude Hannoun, and Jean Marie Cohen, “Sensitivity, Specificity, and Predictive Values of Health Service Based indicators for the Surveillance of Influenza A Epidemics,” International Journal of Epidemiology, (1994) Vol. 23 No. 4 pg. 849-855.
49. Ibid., 29.
50. Quenel, et al., 3.
51. James Gallo, “Operations and Maintenance in a Data Warehouse Environment,” DM Review Magazine, December 2002. See <http://www.dmreview.com/article_sub.cfm?articleId=6118>, accessed March 2004.
52. Mimi Hall, “Bugs, weeds, houseplants could join the war on terror,” USA Today, May 27, 2003. See <http://www.usatoday.com/news/nation/2003-05-27-bugs-cover_x.htm>, accessed March 2004.
53. See <http://www.talkabouthealthnetwork.com/group/alt.psychology.jung/messages/37768.html>, accessed March 2004.
54. Lakshmi Sandhana, “Greenery on Alert,” The Christian Science Monitor, May 1, 2003. See <http://search.csmonitor.com/2003/0501/p12s01-stct.html>, accessed January 2004.
55. Kenneth Chang, “Ideal Sensors for Terror Attack Don’t Exist Yet,” New York Times, April 1, 2003. See <http://www.ph.ucla.edu/epi/bioter/idealsensorsnotexist.html>, accessed January 2004.
56. Maryann Mott, “Dogs of War: Inside the U.S. Military’s Canine Corps,” for National Geographic News, April 9, 2003, access at <http://news.nationalgeographic.com/news/2003/04/0409_030409_militarydogs.html>.
57. Ibid.
58. See <http://www.cnn.com/2001/COMMUNITY/09/20/siegrist/>, accessed February 2004.
59. “US Marines Enlist Pigeons to Detect Iraqi Gas,” Reuters Health, Camp Inchon, Kuwait, March 14, 2003. See <http://yourhealth.healtheast.org/HealthNews/reuters/NewsStory0314200324.htm>, accessed January 2004.
60. Ibid.
61. Ibid.
62. “Keeping the water safe”; MSNBC/The Business Journal of Milwaukee
October 20, 2003, Becca Mader; <http://famulus.msnbc.com/famuluscom/bizjournal10-25-010753.asp?bizj=MIL>.
63. MIT News, “MIT sensor detects pathogens quickly and accurately,” July 10, 2003. See <http://web.mit.edu/newsoffice/nr/2003/sensors.html>, accessed May 2004.
64. Todd H. Rider, et al., “A B Cell-Based Sensor for Rapid Identification of Pathogens,” Science 2003 301: 213-215.
65. http://www.cnn.com/2003/HEALTH/07/10/finding.germs.ap/
66. Ibid., 2.
67. Ibid., 2.
68. Christopher Helman, “Sharpening Our Senses,” Forbes (April 14, 2003) vol. 171, no. 8, p. 56.
69. Ibid., p 56.
70. Oak Ridge National Laboratory FactSheet, March 17, 2003, UT-Battelle.
71. “Oak Ridge Technology Stands Guard Over Water Supplies, “Inside Energy, June 24, 2002, p17.
72. Corrie Brown, Mark Thurmond. “Bio- and Agroterror: The Role of the Veterinary Academy.” Journal of Veterinary Medical Education. Vol 29 no. 1 2002. pp. 1-4.
73. Ibid., 32.
74. Brown and Thurmond, 32.
75. Elizabeth Weise, “Pet ailments could signal toxic attack,” USA Today, 4 April 2003, access at <http://www.delawareonline.com/newsjournal/life/mindbody/2003/04/07petailmentscoul.html>
76. Weise, 35.