October 26 Bioterrorism Update

1. Authorities acknowledge that nasal sampling for spores has a very low yield, in agreement with an animal study that suggested spores only remain in the nostrils for 24 hours after an exposure. Nasal swabs may therefore provide some Information on whether an anthrax exposure occurred recently, but are entirely unreliable in identifying individuals at risk for inhalation anthrax.

2. As I suggested earlier, now that more aggressive environmental sampling has begun, many more areas of anthrax contamination are being identified. Some of these areas may have been contaminated by previously identified anthrax letters, but in many cases the source of contamination has probably not been identified. That means people may still be coming into contact with spores from additional letters, or from other sources.

3. Appropriate antibiotic treatment has now been instittued for 11,000 postal workers and others with suspected significant exposures: 60 days of oral antibiotics. This gives us time to learn whether additional treatment may be required.

4. Postal workers are using HEPA masks and gloves (also suggested by me earlier) and appropriate measures are being taken to decontaminate mail.

5. Government authorities are acknowledging the difficulties inherent in decontaminating offices contaminated with anthrax.

6. CDC recently suggested anthrax vaccination for individuals who were allergic to antibiotics used for anthrax post-exposure prophylaxis. This is medically unsound, and is in conflict with the package insert for the vaccine. Since it takes one month or more to achieve measurable immunity from vaccination, and anthrax can kill in days, immunity generated from the vaccine is entirely inadequate to protect people soon after an exposure.

7. A suggestion made yesterday was to vaccinate Washington DC postal workers. HHS Secretary Tommy Thompson has said that the vaccine manufacturer will be fully licensed by November 22, 2001. If this takes place, expect to see huge numbers of civilians becoming chronically ill afterward. Because Bioport, the vaccine manufacturer, has no commercial insurance, and is instead indemnified for any lawsuits by the Secretary of the Army, the American taxpayer will be footing the entire bill for these illnesses.

If you are offered anthrax vaccine as an experimental product, it will almost certainly be vaccine that was previously quarantined by FDA and/or failed "supplemental" testing mandated by the Secretary of Defense. My guess is that those receiving this product will either be asked to sign a waiver preventing them from suing in the event of vaccine-induced illness, or that the "experimental" nature of the relabeled vaccine will be used to preclude such lawsuits. Caveat emptor: let the buyer beware.

8. What about other treatments?

a. ANTITOXIN/ANTISERUM I just discovered that Dr. Renata Engler, in her May 1999 talk on anthrax vaccine reactions, also suggested antiserum as a possible treatment for those with adverse vaccine reactions, in lieu of further vaccination. A variety of antisera should be manufactured and tested asap, since we do not know which antibodies will be most effective for treatment. Others are likely to be found helpful in the development of new, rapid diagnostic measures. It may be that specific antisera directed against one or more toxin components, or other virulence factors, will be most effective in the treatment of late inhalation anthrax. Or there may be a role for nonspecific antisera directed against vegetative organisms, perhaps earlier in the course of illness. This might slow down the course of illness, allowing other treatments more time to work.

b. PLASMAPHERESIS This expensive and cumbersome treatment, used for certain blood and rheumatological disorders, can potentially remove toxins from the blood, and might have a role in the treatment of late anthrax cases. It too needs to be investigated asap.

c. MONOCLONAL ANTIBODIES If you find the right one(s), this treatment has the potential to be the "silver bullet"--binding only to toxin, or to a critical component of the bacteria, stopping the infection in its tracks. Monoclonals are often useful for rapid diagnostic tests as well. I suggest that a small army of technicians create a complete library of monoclonals against every possible anthrax epitope, and perform animal testing to identify those which are effective in treating anthrax infections in rodents. (And test the others for potential use in diagnostic kits.)

d. LAVAGE I continue to wonder whether bronchoalveolar lavage might help by providing an estimate of ungerminated spores in the lung, and possibly by inducing germination of spores while on adequate treatment. Although this seems paradoxical -- why would you want to increase the body burden of germinated organisms? -- it is important. In the single monkey study in which monkeys received antibiotics for 30 days after a lethal inhaled anthrax dose, 80% of the monkeys survived during antibiotic treatment. But 21% of the survivors succumbed over the following month, after antibiotics were stopped. Autopsy revealed that the monkeys had ungerminated spores remaining in their lungs, which apparently germinated after antibiotics were stopped. Until the spores germinate, they are not killed by antibiotics. Therefore, getting rid of still-viable but ungerminated spores in the lung should be a priority. 60 days of antibiotics might be adequate, but there has been no study to show this yet, so we still are not sure for how long to treat with antibiotics.

9. What about early diagnosis?

a. Is there a role for mediastinoscopy in making the diagnosis prior to culture? A fiberoptic instument could sample the earliest affected area: the mediastinal lymph nodes, and probably the diagnosis could be made with a very simple technique such as gram stain or immunofluorescence.

b. Is CT or MRI of the mediastinum worthwhile for earlier identification of the enlarged nodes that can be very difficult to see on routine chest X-rays? This needs to be studied asap.

c. PCR for anthrax epitopes performed on urine would be a wonderful, noninvasive diagnostic tool. Studies should be instituted asap to see whether such epitopes can be identified. There might even be other, cheaper methods of identifying anthrax in urine.

d. Similarly, we should be aggressively seeking similar epitopes in blood that could be used in rapid diagnostic tests.

e. Do spores survive in the larynx or bronchi longer than in the nose? If so, there might be a role for diagnostic laryngoscopy or bronchoscopy in selected cases.

10. What do we do now? Accurate, available, rapid and sensitive *environmental* diagnostic kits remain the Number One means by which we will be able to cope with anthrax. The best candidates must be put into production immediately, with the expectation that large numbers of these devices might be required. Since it has become clear that the anthrax being used came from a sophisticated lab, there is good reason to assume that other biowarfare agents such as smallpox (but many others have also been produced, in a number of nations) may also be available to the terrorist(s). Methods for identifying other pathogens in environmental samples also need to be assessed, and the best readied for production. Better, safe vaccines should be developed for these threat agents. Existing vaccines, which were never put into clinical trials, should begin small scale, Phase 1 safety testing. Multivalent antisera, monoclonals, and immune enhancing therapies should be developed for other potential agents that can be used in bioterrorism. Antiviral agents need to be tested immediately against viral pathogens to determine the best treatment strategies, in case these viral diseases are seen.

Meryl Nass, MD