Terrorist use of biologic agents.

Thomas E. Collins MD, FACEP

Department of Emergency Medicine

MetroHealth Medical Center

 

It is clear from recent events that the threat of biologic agents being used in our society is no longer mere speculation.  Event are unfolding that demonstrate the intentional use of anthrax spores in over three states, prompting evaluation of hundreds of potentially exposed patients.  For the first time in the United States, physicians at the community level will be expected to become soldiers in the battle against bioterrorism.

 

The threat of biologic agents is not new, and in fact, biologic agents have been employed as a weapon of war for centuries. During the siege of Kaffa (present Ukraine) in the14th Century a plague outbreak occurred among the attacking forces.  Recognizing the potential benefit of infecting the army defending the city, soldiers who had succumbed to the plague were catapulted into the city.  A plague epidemic soon erupted and the defending forces retreated.

 

June 24, 1763 during the French and Indian War, Captain Ecuyer gave contaminated material from a smallpox hospital to natives.  In his journal he recorded "I hope it will have the desired effect."

 

In the more recent past in this country alone, biologic agents were used covertly.  In Oregon in 1984, members of a religious cult deliberately contaminated salad bars with salmonella typhi. produced at the commune.  751 patients were affected.   Pastries left in a Texas medical center break room in 1996 were contaminated with shigella, infecting 12 employees.  The strain was traced back to laboratory stock.

 

Modern warfare using biologic agents is far from science fiction.  Iraq is known to have developed, produced and weaponized over 19,000 liters of botulinum toxic and 8,500 liters of anthrax.  The former Soviet Union had multiple facilities and hundreds of scientists dedicated to weaponizing biologic agents.

 

Anthrax

There are three clinical forms of anthrax:

·        Cutaneous infection occurs when spores contact non-intact skin.  Lesions will initially appear within 12 days of exposure and manifest as pruritic macules or papules with extensive local tissue edema.  A thick, depressed black eschar appears which falls off in 1-2 weeks.  Mortality can reach 20% if untreated due to systemic disease. 

·        Gastrointestinal anthrax is the result of ingestion of contaminated undercooked meat.  Symptoms begin within 1-7 days and consist of severe abdominal pain followed by fever and septicemia.

·        Inhalation anthrax carries the most lethal consequence.  Typically a 2-phase illness, initial symptoms include fever, myalgias, malaise, cough, headache, and chest pain.  After a brief period of slight improvement in some patients, the second stage includes worsening shock, dyspnea, diaphoresis and fever.  Hemorrhagic meningitis occurs in approximately 50% of patients.

 

Transmission

Primate data suggests that the LD₅₀ for humans is inhalation of 2,500 to 55, 000 spores. Once inhaled, these 1-5 micron spores are deposited in the lower respiratory track.  Up to 60 days later, the spores can be phagocytized and transported to mediastinal and hilar lymph nodes.  There the spores germinate into vegetative bacilli and produce a necrotizing hemorrhagic mediastinitis.  Person-to-person spread of anthrax is extremely unlikely and standard universal precautions should be followed.

 

Diagnosis

Clinical diagnosis of inhalational anthrax is based on the presentations previously discussed emphasizing the importance of recognizing mediastinal involvement and the significance of hemorrhagic meningitis.  Suspicion of an intentional release of anthrax spores should be raised when multiple patients are encountered with similar clinical features. Definitive laboratory diagnosis locally may be difficult, but suspicion should be raised with the identification of large amounts of gram-positive bacilli on an unspun peripheral blood smear or rapid growth of large non-hemolytic gram-positive bacilli with preliminary identification of Bacillus species.

 

Treatment of clinical disease and exposure

Current therapy for documented anthrax infection recommendations include ciprofloxacin (400 mg IV q 12 hrs) or doxycycline (200 mg IV load, followed by 100 mg IV q 12 hrs) as initial therapy, with penicillin (4 million U IV q 4 hours) as an alternative once sensitivity data is available.  Therapy may then be tailored once antibiotic sensitivity is available to penicillin G or doxycycline.  Recommended treatment duration is 60 days, and should be changed to oral therapy as clinical condition improves.  Supportive therapy for shock, fluid volume deficit, and adequacy of airway may all be needed.

 

Post-exposure prophylaxis.

One of the key factors in determining the need for antibiotic prophylaxis is the credibility of the exposure.  There are a tremendous amount of "hoax" events occurring both locally and nationally.  Local law enforcement agencies will coordinate with the FBI to determine the credibility of the threat and if further investigation is warranted.  Communications should occur with the local health department to ascertain details of the exposure and current recommendations before any antibiotics are prescribed.

 

If post-exposure prophylaxis is recommended, ciprofloxacin (500 mg bid) or doxycycline (100mg bid) should be initiated for the first 48-72 hours to all adults (including pregnant women) while sensitivities are determined.  Pediatric patients follow the same antibiotic regime with weight specific dosing until sensitivities are known.

 

SMALLPOX

Smallpox also represents a significant risk to our population.  One single identified case of smallpox in a national public health emergency.  Little of the population has any immunity, even if childhood vaccination was performed. Clinical manifestations begin acutely with malaise, fever, rigors, vomiting, headache, and backache. 2-3 days later lesions appear which quickly progress from macules to papules, and eventually to pustular vesicles. They are more abundant on the extremities and face, and develop synchronously.  Patients are contagious once the rash develops.

 

Electron and light microscopy are not capable of discriminating variola from vaccinia, monkeypox or cowpox. The new PCR diagnostic techniques may be more accurate in discriminating between variola and other Orthopoxviruses.  At present there is no effective chemotherapy, and treatment of a clinical case remains supportive.

 

Prophylaxis care revolves around immediate vaccination or revaccination should be undertaken for all personnel exposed. Vaccinia immune globulin (VIG) is of value in post-exposure prophylaxis of smallpox when given within the first week following exposure.  Droplet and Airborne Precautions for a minimum of 16-17 days following exposure for all contacts. Patients should be considered infectious until all scabs separate.

 

There are numerous sources for additional and up-to-date information.  These include:

 

·        Centers for Disease Control www.bt.cdc.gov (includes links to other useful sites).

·        Ohio Department of Health www.odh.state.oh.us/ODHPrograms/DisPrep/disprep1.htm

·        Cuyahoga County Board of Health www.ccbh.net

·        AMC/NOMA www.amcnoma.org

 

Anthrax and smallpox are two of many potential biologic agents that may be utilized as weapons.  Other agents include plague, botulinum toxic, viral hemorrhagic fever, tuleremia and numerous others. 

 

Local preparation and response to this new era of medicine includes the combined efforts of the physician community, medical centers, public health departments, and public safety forces.  Plans will need to be dynamic and able to react to the wide variety of potential threats and presentations.  Physicians play a crucial part as role models for our entire community.  Every effort should be dispel myths our patients may have and reduce their fears.

 

AMC/NOMA will play a critical role in coordinating with other response agencies, providing information for our patients, and educating the medical community.  One of these events will be a CME course sponsored by CWRU School of Medicine “Biologic & Chemical Terrorism “What Health Care Professionals Need to Know” held on November 17^th and December 1^st. Contact the Continuing Education Department at

216-368-2408 or 800-274-8263 or visit their website at http://cme.cwru.edu/biochemterrorism.htm.

 

When to suspect a bioterrorist attack?

 

·        Unusual age distribution for common diseases

·        Unusual disease patterns/deaths in animals.

·        Large epidemic with high illness and death rate

·        HIV(+) individuals may have first susceptibility

·        Respiratory symptoms predominate

·        Infection non-endemic for region

·        Multiple, simultaneous outbreaks

·        Multi-drug-resistant pathogens

·        Sick or dead animals of multiple types

·        Delivery vehicle or intelligence information suggestive of threat.

 

 

References

·        CDC.Update:Investigation of Antrax Associated with Intentional Exposure and Interim Public Health Guidelines.   MMWR 2001, Vol. 50, Number 41. 

·        Inglesby TV, Henderson DA. Antrax as a Biological Weapon.  JAMA. May 1999;281:17441745

·        Office of the Surgeon General, Department of the Army, USA, Textbook of Military Medicine, Medical Aspects of Chemical and Biological Warfare. Washington DC