Pharmacists Can Calm and Educate the Public

Bioterrorism Information

Anthrax Summary

Amy C. Hannig and Tracy Hetzner, Pharm.D. Candidates, Ohio Northern University and OPA Externs

Anthrax is an acute infectious disease caused by the large, gram-positive, encapsulated, spore-forming bacterium Bacillus anthracis. First appearing in animal skins in 1500 B.C., this infectious agent has reemerged in the biological terrorism currently plaguing America.
Forms and Symptoms. The disease originates from ingesting, inhaling or physically contacting anthrax spores through an open wound. Regardless of how the spores are contracted, immediate antibiotic treatment is imperative. There are three forms of anthrax infections: gastro-intestinal (GI), inhalation, and cutaneous.

The intestinal form of anthrax is characterized as an acute inflammation of the GI tract. Initial symptoms include nausea, decreased appetite, vomiting or fever. Abdominal pain, vomiting of blood and severe diarrhea may occur in later stages. Although this form of the disease is quite rare, death rates vary between 25 and 60 percent.

The disease progression of inhaled anthrax is biphasic. Once a person has inhaled anthrax, he/she will experience non-contagious flu-like symptoms for four days including a low-grade fever, non-productive cough, malaise, myalgia, headache and mild chest pain. This first phase is concluded with a one to three day period of symptomatic improvement. The second phase drastically takes hold with sudden onset acute respiratory distress due to enlarged mediastinal lymph nodes compressing the trachea, and continues with cyanosis, shock, fever, pleural effusion and death within 24 to 36 hours. If untreated, the chance of survival is a mere 10 percent. Exposure can be confirmed with a nasal swab or blood smear and treated effectively with antibiotics.

The cutaneous form of anthrax is the most common type, at 95 percent of past reported cases. Physical contact with anthrax can lead to an erythemous lesion resembling an insect bite (raised itchy bump). After several days, the center of this subcutaneous reaction blackens. Cutaneous anthrax symptoms are readily recognizable. This form of the disease is easily treated with antibiotics, and rarely results in death.

Diagnosis. Anthrax is diagnosed by isolating Bacillus anthracis from blood, skin lesions or respiratory secretions, or by measuring specific antibodies in blood.

Treatment. Although penicillin is considered the drug of choice to treat naturally occurring anthrax, penicillin-resistant strains exist. In July 2000, FDA approved ciprofloxacin (Cipro�, Bayer) to manage the intentional use of anthrax as a biological agent for use in people exposed to inhaled anthrax. For adults, FDA recommends 500mg by mouth twice daily for 60 days. Although ciprofloxacin is currently not approved for children (for non-anthrax related disorders) due to its potential adverse effects on cartilage, this effect has never been conclusively proven in humans. For pediatrics, dosing is15mg/kg by mouth twice daily for 60 days. Most common adverse reactions include nausea, vomiting, diarrhea, abdominal pain, rash, headache and restlessness.

As of October 18, 2001, doxycycline is seeking the approval from FDA to treat all types of anthrax. The dosing regimen will include 100mg every 12 hours for adults, and 1mg/lb every 12 hours for children weighing less than 100 pounds.

There is concern that, with the increased use of ciprofloxacin, the causative organisms may eventually become resistant to this antibiotic as well. Due to past resistance of the bacteria to penicillin, tetracycline and erythromycin, these antibiotics are currently not recommended for first-line use. It is speculated that the current infectious organisms are probably manufactured to be resistant to these three antibiotic agents.

Vaccines. There are two types of human vaccines available in the United States. These vaccines are �cell-free filtrate vaccines.� In other words, there is neither dead nor live bacteria in these vaccines. The vaccines are approximately 93 percent effective when administered correctly. The current administration protocol involves three subcutaneous injections (0.5mL) given two weeks apart, followed by three additional subcutaneous injections given at six, 12, and 18 months. Annual booster injections of vaccine are recommended thereafter. Only 30 percent of patients experience mild local adverse reactions, including tenderness, swelling, and redness at the injection site. However, because anthrax is not contagious, the current supply of vaccines is reserved for those persons who are likely to come in direct contact with the causative agent.
Person-to-person transmission does not occur with inhalation or GI anthrax. It is important to educate patients that the flu vaccine will not prevent anthrax.

Selected References:
1. Bacillus Anthrax. CDC Information Sheet. www.cdc.gov
2. Hot Topic in Healthcare. American Health Consultants. www.ahcpub.com
3. FDA will approve new labeling for antibiotics to treat anthrax. Reuters Medical News for the Professional. 18 Oct. 2001. www.medscape.com
4. Approval of Cipro for use after exposure to inhalation anthrax. FDA Talk Paper. www.fda.gov

National Pharmaceutical Stockpile
The mission of CDC�s National Pharmaceutical Stockpile (NPS) program is to ensure the availability of life saving pharmaceuticals, antibiotics, chemical interventions, as well as medical, surgical and patient support supplies, and equipment for prompt delivery to the site of a disaster, including a possible biological or chemical terrorist event anywhere in the United States. The NPS is available to supplement the initial response to an incident of biological or chemical terrorism. That response will come from local and state emergency, medical and public health personnel. A decision to deploy the stockpile is based on the best epidemiologic, laboratory and public health information regarding the nature of the threat.

Contents of the Stockpile
CDC has established relationships with various national security agencies to facilitate continuous updates and analyses of threat agents and ensure that the NPS reflects current needs. Expert panels convened by CDC prioritized the following biological agents: smallpox, anthrax, pneumonic plague, tularemia, botulinum toxin and viral hemorrhagic fevers. Because anthrax, plague and tularemia can be effectively treated with antibiotics that are immediately available, purchasing these products for the NPS formulary was given first priority. The NPS also has a cache of vaccine available to address smallpox threats. In addition to medications and supplies for intravenous administration, the NPS includes medical equipment that would be essential for treatment, including airway supplies, bandages and dressings, and other emergency medications. These are items that local clinicians may find in short supply in the event of a terrorism incident.

Components of the National Pharmaceutical Stockpile
The National Pharmaceutical Stockpile (NPS) has two basic components. The first component consists of eight 12-hour Push Packages for immediate response. These 12-hour Push Packages are fully stocked, positioned in environmentally controlled and secured warehouses, and ready for immediate deployment to reach any affected area within 12 hours of the federal decision to release the assets. A 12-hour Push Package is a preassembled set of supplies, pharmaceuticals, and medical equipment ready for quick delivery to and use in the field. Each �package� consists of 50 tons of material intended to address a mass casualty incident. These packages will permit emergency medical staff to treat a variety of different agents, since the actual threat may not have been identified at the time of the stockpile deployment.

The second component is comprised of Vendor Managed Inventory (VMI) material. If the incident requires a larger or multi-phased response, follow-on VMI Packages will be shipped to arrive within 24 to 36 hours. The follow-on VMI packages are comprised of pharmaceuticals and supplies that can be �tailored� to provide pharmaceuticals, supplies and/or products specific for the suspected or confirmed agent or combination of agents.

Pharmacists Can Calm and Help Educate the Public
Internet Pharmacies Promoting the Sale of Antibiotics to Combat Antrax. In response to the terrorist attacks of September 11, 2001, and the threat of bioterrorism, the American Pharmaceutical Association (APhA) warns that some disreputable Internet pharmacies are offering consumers antibiotics, purportedly to fight anthrax infection, without requiring a physician�s prescription.�The integrity of Internet antibiotics cannot be assured; the product could be a counterfeit, contaminated, expired or without active ingredients.

APhA is also concerned about the widespread use and stockpiling of antibiotics acquired through normal distribution channels. Unnecessary stockpiling may make it more difficult to assure adequate supply in the event of a more widespread incidence of anthrax exposure or other infection.� Stockpiling also raises concerns about expiration dating and varying storage conditions of the medicine.

Ohio Health Alert Advisory. Dr. Forrest Smith, State Epidemiologist with the Ohio Department of Health, is recommending that physicians do not prescribe prophylactic antibiotics in response to bioterrorism fears. If the situation changes, the medical community will receive guidance. In a September 20, 2001 Health Alert Advisory, he stated that the indiscriminate prescribing of antibiotics is not warranted. There are no antibiotics or vaccines that cover all potential biologic agents. Having these antibiotics in the home could also predispose people to self-medicate for other illnesses instead of seeking appropriate medical care and delaying evaluation and treatment. There is also concern about increasing resistance of common infection-producing bacteria with inappropriate use of antibiotics.

CDC Guidelines for State Health Departments
Revised October 14, 2001

Advice to the Public
How To Handle Anthrax and Other Biological Agent Threats. Many facilities in communities around the country have received anthrax threat letters. Most were empty envelopes; some have contained powdery substances. The purpose of these guidelines is to recommend procedures for handling such incidents.

DO NOT PANIC
1. Anthrax organisms can cause infection in the skin, gastrointestinal system, or the lungs. To do so, the organism must be rubbed into abraded skin, swallowed, or inhaled as a fine, aerosolized mist. Disease can be prevented after exposure to the anthrax spores by early treatment with the appropriate antibiotics. Anthrax is not spread from one person to another person.
2. For anthrax to be effective as a covert agent, it must be aerosolized into very small particles. This is difficult to do, and requires a great deal of technical skill and special equipment. If these small particles are inhaled, life-threatening lung infection can occur, but prompt recognition and treatment are effective.
Suspicious Letter or Package
1. Do not shake or empty the contents of any suspicious envelope or package; DO NOT try to clean up powders or fluids.
2. PLACE the envelope or package in a plastic bag or some other type of container to prevent leakage of contents.
3. If you do not have any container, then COVER the envelope or package with anything (e.g., clothing, paper, trash can, etc.) and do not remove this cover.
4. Then LEAVE the room and CLOSE the door, or section off the area to prevent others from entering.
5. WASH your hands with soap and water to prevent spreading any powder to your face or skin.
6. If you are at HOME, report the incident to local police. If you are at WORK, report the incident to local police, and notify your building security official or an available supervisor.
7. If possible, LIST all people who were in the room or area when this suspicious letter or package was recognized. Give this list to both the local public health authorities and law enforcement officials for follow-up investigations and advice.
8. REMOVE heavily contaminated clothing and place in a plastic bag that can be sealed; give the bag to law enforcement personnel.
9. SHOWER with soap and water as soon as possible. Do not use bleach or disinfectant on your skin.

CDC Bioterrorism Website: www.bt.cdc.gov

CDC Bioterrorism-related phone line for questions about antrax and small pox: 404.639.2807404.639.2807

Beware of Attempted Potassium Permanganate Purchases

A pharmacist at a store in suburban Raleigh, NC was approached on September 28, 2001 by several suspicious looking men, one of whom asked to purchase potassium permanganate. While potassium permanganate has a medical use, it can also be used as an ingredient in an explosive mixture. Other products available in pharmacies such as potassium nitrate, potassium chlorate, potassium perchlorate, ammonium nitrate, sulfur, charcoal and acetone may also be used for that purpose. The recent incident has been reported to the FBI.

Pharmacists are cautioned to be alert for this activity and to be certain that any such purchases are for a legitimate medical purpose. Case law (Kruger v. Knutson, 111 N.W. 2nd 526) has held pharmacists responsible for selling such chemicals when injury occurs later. This notice is intended to guide you in your professional conduct.