Anthrax in a BioWar Environment

by Sheldon Campbell, MD

ANTHRAX IN A BIOWAR ENVIRONMENT

Sheldon Campbell MD, PhD 12/2/90

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The following document is derived entirely from the open medical literature and my clinical (and to a certain extent, tactical and political) judgement. There are two important limitations to the following data. First, I am a medical microbiologist, not a clinical infectious disease specialist. Although the information is derived from an exhaustive review of the available medical literature, and I doubt that an ID person would significantly modify my conclusions, there's a limit to the usefulness of knowledge derived entirely from the literature. I've tried to indicate places where this might be important. Second, I have no access to any classified information, nor even to much of the open military literature. Information on the nature of the potential biological threat might supersede anything I say here.

DISSEMINATION AND INFECTION

It is expected that anthrax spores will be disseminated by the aerosol route, causing inhalation anthrax. Because atmospheric stability is important to efficient spread, and because sunlight is highly toxic to biological agents, they are most likely to be delivered at night. Particles from 1 to 5 microns in size are most efficient in causing infection, and can be present in clinically significant quantities more than 20 km downwind. The inhaled infectious dose in man is quite high (est >3,000) -- nonimmunized workers in animal-hair mills have been shown to inhale 150-700 infected particles/hour <=5 microns, but are rarely affected. The addition of detergents, irritants, or immunosupressives to the aerosol may decrease the infective dose needed by up to 10-fold. It's likely that heavy smokers would be more susceptible, and to larger particle sizes. There is no data available on this, however.

CLINICAL PRESENTATION AND DIAGNOSIS

Inhalation anthrax (also known as Woolsorter's disease) is a biphasic illness. The first phase occurs when the spores are carried to the mediastinal lymph nodes by pulmonary macrophages and cause a suppurative infection with edema and hemorrhage. This phase is characterized by nonspecific flu-like symptoms; mild fever, malaise, fatigue, myalgia, nonproductive cough, and at times a sensation of chest oppression or pressure. Rhonchi may be heard with a stethoscope. The presence of such symptoms in a large number of personnel at once should raise the suspicion of anthrax. This phase can last for several days, or for as little as 24 hours in heavy infections, and can be followed by an asymptomatic period. A helpful radiographic sign is symmetrical enlargement of the superior mediastinum due to lymph node enlargement. The disease is treatable in this stage, but blood cultures are probably negative (no data on this). Sputum cultures might have a higher yield, particularly if anthrax is specifically looked for.

The second phase develops suddenly with the development of severe shortness of breath and cyanosis. Hypotension and shock occur. The temperature may be elevated or subnormal due to shock, and perspiration is often profuse. Stridor may be present due to enlargement of the lymph nodes near the trachea. Chest exam shows moist, crepitant rales and signs of pleural effusion. Blood cultures are positive, and the bacteremia may be high enough for organisms to be visible on a Gram stained smear. The second, acute phase typically lasts less than 24 hours and usually ends in death despite therapy, due to the high number of toxin-producing organisms present by this stage in the illness.

RECOMMENDATIONS FOR THERAPY

The standard therapy for inhalation anthrax is intravenous penicillin G by continuous infusion, 50 mg/kg or 80,000 U/kg in the first hour, followed by 200 mg/kg or 320,000 U/kg over the following 24h. No data are available on the value on penicillin IM, but it would likely be less effective and larger doses might be required. Streptomycin, 1-2 g/24h IM has been described to be synergistic in combination with penicillin. An alternative regimen is erythromycin, 4g/24h by continuous infusion. In a biological warfare situation, however, I would recommend that vancomycin be a part of any regimen, in a dose of 500 mg every 6 hours. Intramuscular injection of vancomycin is painful. An inferior but possibly useful substitute for vancomycin would be oxacillin, methicillin, or nafcillin in appropriate dosages (use the PDR). Other drugs to which B. anthracis is generally considered susceptible include the first-generation cephalosporins, tetracycline, and chloramphenicol. Adjuvant therapy with hydrocortisone, 100-200 mg/day may be helpful in the case of malignant chest-wall and neck edema. As soon as in vitro susceptibility data are available, therapy should be adjusted to include effective drugs, and drugs to which the isolate is resistant should be eliminated.

In animal models, therapy for less than 2 weeks was ineffective due to persistence of infective spores in the lungs -- no data are available in humans. If antibiotics are present in limited quantities, the least ill patients should be treated first, as patients in the second phase of the illness have a poor prognosis even with effective therapy. I do not agree with the recommendation of Col. Wiener (see below) of creating test groups to be treated each with only one drug to see which works. Unless communications and support services degenerate to a point of complete chaos, in vitro susceptibility testing will provide equivalent data more rapidly. It is, however, appropriate to treat as many people as possible with whatever antibiotics if limited quantities are available.

RATIONALE FOR THERAPEUTIC RECOMMENDATIONS

Some discussion of these recommendations is in order. Most clinical isolates of anthrax are penicillin-susceptible. Virulent strains resistant to penicillin have been described at least since 1970, however. Because penicillin is cheap, it is likely that any strain used for biological warfare will be penicillin-resistant. Most penicillin-resistant organisms do so by producing beta-lactamases. The oxacillin group of semisynthetic penicillins are resistant to many beta-lactamases, thus the recommendation of these drugs as an alternative to vancomycin.

On the other hand, vancomycin resistance, except for a few strains of enterococcus, is primarily a rare laboratory phenomenon. In addition, vancomycin is an expensive compound and it would be prohibitive to produce industrial quantities of resistant organisms. Thus vancomycin should be considered the gold standard of empirical therapy in a biowar environment. Similarly, developing and producing a strain resistant to both erythromycin and penicillin would more than double the cost and difficulty of producing the bugs unless fairly sophisticated molecular techniques were employed. If I were running things for the Iraqis, I'd be using a penicillin-resistant strain without any other modifications, since each piece of genetic baggage the organism has to carry will have unpredictable effects on virulence, and it's a very effective weapon already.

EARLY WARNING, IMMUNIZATION, AND REFERENCES

REQUEST FOR INFORMATION:

Early warning is possible to biological attacks. Radar can detect aircraft flying suspicious attack patterns. There are descriptions in the literature of air-sampling arrangements which can be combined with microculture or immunoassays to provide rapid identification of an attacking organism. I have no idea what's currently being done -- can anyone help out here without betraying secrets?

REQUEST FOR INFORMATION:

Anthrax vaccines are available and have been given to high-risk groups such as textile workers. I have no data about what's going on in Desert Shield -- surely this at least is open information (it'd be hard to hide).

REFERENCES

Manchee RJ et al (1981), Bacillus Anthracis on Gruinard Island, Nature 294, 254-255.

Manchee RJ et al (1983), Decontamination of Bacillus Anthracis on Gruinard Island?, Nature 303, 239-240.

Wiener SL (1987), Strategies of Biowarfare Defense, Military Medicine 152, 25-28.

Brachman PS (1980), Inhalation Anthrax, Proc. NY. Acad. Sci., 83-93.

Knudson GB (1986), Treatment of Anthrax in Man: History and Current Concepts, Military Medicine 151, 71-77.

Multiple Authors (1963), Defense Against Biological Warfare -- A Symposium, Military Medicine 128, 81-146.

Health Aspects of Chemical and Biological Weapons, Report of a WHO Group of Consultants, World Health Organization, Geneva, Switzerland, 1970.