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Anthrax, Separating Fact from Fiction, Pg. 2 The genesis of anthrax
infection Phagocytosis is the normal process whereby the body's cells which normally fight infection and 'clean house' ingest foreign matter or cell fragments, kill the material, digest it, and ultimately dispense with it as an innocuous substance which the body can handle. The ability of anthrax to do an end run around this normal process is attributed to a specific acid capsule, poly-D-glutamic. Like many bacteria, anthrax thrive in nutrient-rich environments like tissues or blood. Thus, once they are able to enter the bloodstream, they multiply rapidly. Also like other bacteria, anthrax bacteria produce protein toxins. In the case of anthrax, there are three such toxins that have been identified -- protective antigen (PA), edema factor (EF), and lethal factor (LF). This is what accounts for the high virulence of anthrax. In cutaneous anthrax, the bacterial spores begin to germinate within hours, eventually resulting in necrotic skin lesions. Even left untreated, however, only about 20% of cutaneous anthrax cases are lethal. In the rarer gastrointestinal anthrax, which is almost always lethal, the bacteria can survive passage through the stomach and initiate infection in the intestines. But there is also an even more rare form -- oropharyngeal anthrax -- that can cause a primary infection much higher in the GI system. Curiously, in inhalational anthrax, at least one problematic element of the infection seems to stem from a partial success of the body's natural defense, whereby some of the spores are ingested by phagocytosis, but ultimately carried to lymph nodes in the mediastinum [the mid-line area of the chest cavity] where they then germinate. Once this migration has occurred, infection spreads rapidly, damaging the nodes by hemorrhage and necrosis [decay], and quickly overloading the bloodstream [bacteremia]. Symptoms
of anthrax First, and one of the single most problematic pieces of the puzzle of anthrax from a public health management standpoint, is the fact of anthrax's highly virulent character. If anthrax is contracted, it is important that treatment begin immediately. The other factor, however, has to do with the early signs of inhalational anthrax, which can mimic symptoms of colds or flu. According to Harrison's, "The presenting symptoms of inhalational anthrax ... resemble those of severe viral respiratory diseases." Add to that the fact that we are now entering the period when cold and flu symptoms begin to increase, as they do each year, and all this combines to make the effective diagnosis and management of anthrax a formidable task. However, it should be emphasized that, while not definitive, inhalation anthrax is often not accompanied by a runny nose. Harrison's also acknowledges that, while critical, nonetheless, "Early diagnosis of inhalational anthrax that occurs naturally or as a consequence of biological warfare or bioterrorism is difficult." In the past, according to Dr. Swartz, the differential diagnosis of anthrax, i.e., distinguishing anthrax from other conditions which it might resemble, "was made on the basis of clinical findings and the history of exposure to animal products from abroad." Unfortunately, the use of anthrax as an agent of bio-terrorism has changed that. With regard to cutaneous anthrax, there are a number of other skin diseases which need to be ruled out. These include staphylococcal infection, ecthyma [large round pustules on the skin over an inflammed base], orf [lesions casued by a parapox virus which also is found in certain animals and soil], and even the bit of a brown recluse spider. According to Swartz, in inhalation anthrax, there is also the possibility of tularemia to consider. Tularemia is a disease of rodents and rabbits caused by Pasturella tularense that can also infect humans, either when transmitted by a deer fly or by direct contact with the bacteria. And it also results in the widening of the mediastinum otherwise associated with anthrax. According to Harrison's, some 1 to 3 days after the initial infection in inhalation anthrax, the symptoms noted earlier that can resemble a viral respiratory disease are followed by "an acute phase." This subsequent phase is characterized by "increasing fever, dyspnea [difficulty breathing], stridor [the rasping sound on inhalation noramlly associated with croup], hypoxia [decreased oxygen supply to tissues], and hypotension." One of the most prominent signs of inhalation anthrax, however, is the widening of the mediastinum as a result of the migration of the infection to that region. But it is definitively visible only upon x-ray exam. Thus, as with most bacterial infections, the definitive diagnosis of anthrax can only be positively established by culture or similar lab procedures. Nonetheless, given the rapid spread of the infection and its potentially lethal outcome, Dr. Swartz suggests that, nowadays, clinicians work on the assumption of anthrax when one sees "prominent influenza-like symptoms of recent origin in a patient with a widened mediastinum ... particularly if there were more than one such case." Treatment
of anthrax Why, then, is there the focus on Cipro and concern about adequate supplies of antibiotics for the treatment of anthrax? The most likely reason has to do with the pathogenesis of inhalation anthrax, i.e., how the infection spreads after it is introduced. A 1993 article from the Journal of Infectious Diseases -- "Postexposure prophylaxis against experimental inhalation anthrax " -- cited by Swartz in his recent piece, reported results of tests run on Rhesus monkeys which showed that, once transported to the mediastinal lymph nodes, the anthrax bacteria could germinate up to sixty days later. This finding was later confirmed in follow-up work on the anthrax outbreak in the Soviet Union, which was published in The New England Journal of Medicine six years later under the simple title, "Anthrax." And these findings are the primary reason why at least confirmed cases which have tested positive for anthrax are placed on the unusually long 60-day regimen of medication. The problem with such a lengthy treatment regiment, however, is that, with any number of antibiotics, there are often strong contraindications to administering them for that long a period. Penicillin G, for example, is generally not prescribed for more than a two-week regimen, because dosages beyond that have long been associated with neutropenia -- a condition in which there is a decrease in leukocytes, the disease-fighting white blood cells. Moreover, prolonged exposure to PenG has also been associated with serum-sickness like reactions, a type III hypersensitivity response, usually to the injection of large amounts of antigen -- substances that are seen after viral infection but before the virus begins to replicate. Antigens, in reaction with other elements, play an important role in a variety of beneficial outcomes in immune response, including the production of antibodies, cell-mediated immunities, and increased immunologic tolerance. Serum-sickness is thus sometimes seen in passive immunizations. Another drug of choice for the treatment of anthrax has been doxycycline, a member of the tetracycline family. But the tetracyclines have long been contraindicated for young children, because of its effects on tooth discoloration and the erosion of tooth enamel and, more importantly, particularly in premature infants, delays in bone development. But such considerations are weighed against the possible beneficial effects of such treatments when it comes to anthrax. Thus, on October 26th, the FDA published a revised list of drugs and treatment regimens for anthrax that included provisions for re-labeling both Penicillin G and the doxycyclines under the title "Prescription Drug Products; Doxycycline and Penicillin G Procaine Administration for Inhalational Anthrax (Post-Exposure)." The Summary follows:
One last note needs to be sounded when it comes to antibiotic treatment for anthrax. ... As we have now heard from a variety of sources, many people have been stockpiling antibiotics, especially Cipro [ciprofloxacin hydrochloride], which was approved for inhalation anthrax by the FDA a year ago August and, until now, was the only drug specifically approved for that purpose. But some have also begun to take the drug prophylactically, for prevention, a move which could, in the longer run, make things even more difficult than they already are -- both for those individuals and for human beings generally. The reason is that prophylactic use of antibiotics is hardly ever a good idea. First off, any antibiotic is not pathogen-specific, i.e., while some antibiotics are more effective against different types of bacteria than others, all antibiotics act against all bacteria. That is one reason, for example, why antibiotic regimens often result in diarrhea, since the bacteria necessary for proper digestion are killed along with all the rest. But there is an even more important reason not to take antibiotics as a precaution against anthrax, or any other infection for that matter. The use of antibiotics is analogous to the use of pesticides. Over prolonged exposure, the targets of these treatments slowly but surely begin to develop immunities to them. That is one of the reasons, for example, why we have seen so many new brands of penicillin since it was first introduced in the middle of the last century. The bacteria which were originally susceptible to penicillin treatment developed immunities which then required the development of more sophisticated forms of penicillin, or the multiple-antibiotic medications that have become much more common. In short, then, while anthrax is obviously becoming an increasingly legitimate concern, both the relatively few numbers of cases so far and the unlikelihood of exposure, at least to date, mean a little common sense is in order. If you have concerns, of course, you should discuss them with your doctor. A genuine case of inhalation anthrax, as we said, can be lethal. But we also need to be every bit as cautious that we don't overtax the medical resources we have by assuming the worst at the first sign of cold or flu symptoms, or even more, by stockpiling drugs for preventative purposes which, God forbid, others may need much more. Lou Colasanti, Ed. . ******* ******* If you would like to submit something for our Health & Med section, don't hesitate to let us know. Simply e-mail us at health@downstreetmagazine.com. The e-mail should contain your name, address, and a phone number where we can reach you. You may also send a copy of your proposed article. The text can either be included in the body of the e-mail, or you can send it as an attachment in just about any word processing format. If your piece is accepted, we will pay a small honorarium for your interest & your time. [See Freelancers Wanted for more details.] ******* ******* If you would like to advertise in this section, or throughout the magazine, please visit our Advertising Info Pages ... or call, write, or e-mail ads@downstreetmagazine.com. ******* ******* |
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