Possible Scenarios Of Bioterrorism Attacks Distinguishing Victims From Perpetrators

Each of these scenarios must take into account multiple factors and the limitations of any analytic process to be applied. This is often considered by understanding the elements of positive and negative predictive values of an assay within a population being tested. On one extreme is the situation that occurred with the onset of human immune deficiency (HIV) in the U.S. First there were no cases, and therefore a precise highly sensitive and specific test with excellent positive and negative predictive values (such as exists now when a combination of tests are used) would not likely yield a positive result in an area where there was little disease at the onset, Kansas, for example. A positive test by today's methodologies from a 1970 serum sample from Kansas would be considered a probable false-positive and warrant further investigation. However the same sample tested at the beginning of HIV testing could have been positive if the person had adult T-cell leukemia, which is caused by human T-cell leukemia virus-1 (HTLV-1). This is because the original tests for what became known as acquired immunodeficiency syndrome (AIDS) involved whole viral lysates in which up to 30% of the HTLV-1 sera cross-reacted. Suspicion to the contrary would be raised by knowledge of different presentations of the infection. For example, HTLV-1 can actually be used in the laboratory to immortalize cells. In the patient it actually increases the T-cell count, as is the nature with leukemia, instead of decreasing them, as with HIV infections. Other laboratory indicators such as hypercalcemia would now raise leukemia as a consideration.

Interpretation of a positive clinical test must take into account the health status of the person being tested. This is important for the practice of medicine and can have relevance when extended to forensic analysis. The following situations illustrate the concept. Individuals who have syphilis, a bacterial spirochetal infection, can typically have a positive FTA (fluorescent treponemal antibody) test for years. However while infected they would have a positive venereal disease research laboratory (VDRL) test. This reverts to negative with successful antibiotic therapy. There are some notable exceptions related to cross-reactive epitopes or autoimmune diseases. These are readily distinguishable by history and clinical information. Similarly individuals infected with tuberculosis will have a positive skin test (Mantoux), whereas the unin-fected healthy person will be negative. In certain instances, a sick person with a cell-mediated immune deficiency will be anergic, that is, he/she will be negative to multiple skin tests including common antigens such as Candida. The key difference here is that there is a wide difference between the healthy person being tested and a very ill individual being subjected to the same test.

Tests may also discriminate between the time of the infection as acute or chronic, and its limitations may lead to different interpretations unless one is familiar with those limitations. An example of this occurred with the bacterial infection of Borrelia burgdorferi, which causes Lyme disease. Dattwyler's group showed that antibiotics could abrogate the antibody response because ELISA results were negative in 30% of patients with known disease who were treated early.21 Another group showed that in early cases reactivity to a unique antigen, OspA, was also negative in serological assays despite a demonstrable T-cell response.22 Our own group had an opportunity to analyze the same sera and found that there was antibody to B. burgdorferi but it was below the threshold of the conventional assays. It was detectable in its bound form, in immune complexes.23,24

Anthrax can be used as an example where investigatory leads can be generated by considering a scenario in toto. The elderly lady who died in Connecticut from anthrax clearly had no occupational exposure nor was she known to have had contact with anyone who had anthrax. It was possible that she received contaminated mail. However if this case had occurred as the index case or out of context of the mail attacks, it would have been reasonable to question her travel history, what her work if any was, or if she received or used products from an endemic area for anthrax. Similarly the Vietnamese woman who died in New York City would also have had these questions investigated. It would have been useful to search for direct or indirect evidence of anthrax by physical examinations of her contacts or close neighbors. Inspection and cultures from her workplace, apartment, and apartment complex (especially contiguous neighbors) are important for presence of anthrax. Coworkers, friends, neighbors, and other contacts could have had blood samples analyzed for antibody to anthrax antigens. These samples could have been frozen so that if one were positive it would be available for a comparison study in the future. At a minimum these types of studies could serve as future control data for the geographic region. Although hypothetical, several results could have occurred, and each will be analyzed separately: First example: a close contact is positive for IgM to one of the B. anthracis antigens, e.g. PA. This would suggest that this person had recent exposure and if nothing else should be treated. This individual could conceivably be the one who knowingly or unknowingly passed the spores to the patient. Given the October 26 onset of illness, which is late in the mailing sequence, it would be less likely that this individual was a perpetrator but rather a recent victim too. However if this person were IgG-positive on the assay, then there are several other possibilities. Perhaps this person had past exposure in an endemic region with a subclinical or treated illness (e.g., Haiti, where anthrax is known as "charcoal disease"). Or this person could have been vaccinated for bona fide reasons such as a researcher who received it for occupational protection. Or this person could have obtained the vaccine originally for legitimate or illegal purposes but was nevertheless vaccinated. Animal vaccines may be more obtainable without strict record keeping. This person could have loaded the mail with relative impunity if there were protective antibody generated from the vaccine. These situations require intelligence information regarding access, ability, and motive. However the IgG finding could point investigators towards such an individual, whereas an IgM finding justifies critical therapy. Coming from the other direction, where information points to a particular individual, investigation could be extended to ingestion of antibiotics. Questions would be raised regarding access to antibiotics, recent ingestion of them, half-life of the antibiotic, half-life of the metabolites of the antibiotics, and in which body fluids or tissues the residual can be found. As illustrated from the data in the earlier sections, someone with antibiotics in their system could be protected from exposure to a sensitive microbe. This person would be antibody-negative and likely antigen- and microbial DNA/RNA-negative, since the infection would have been eradicated before the organism could proliferate in any significant quantity.

Similar strategies can be employed to examine suspicious but possible accidental transmission of infections. This is illustrated by a recent series of aviant flu. Tools to determine a person to person spread as the transmission mode included viral cultures, serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and

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