The threat of bioterrorism is all too close to home. Are we prepared, and if so, for what exactly should we be preparing?

Bioterrorism is defined as the deliberate or threatened use of bacteria, viruses or toxins to cause disease, death, disruption or fear. Biological weapons have distinct advantages over traditional weapons. Attacks can be made against a large area in a short period of time using aerosolized biological agents. The detection of the biological release would most likely be delayed since these agents are odorless, colorless and tasteless.

Today, experts predict the most likely method of biological attack would be a large-scale use of an aerosolized agent that may or may not be contagious. The diseases produced by biological agents all present very similar symptoms. In the beginning, symptoms are usually non-specific and flu-like, which makes early diagnosis difficult.

Most likely agents

The Centers for Disease Control (CDC) and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) narrowed the list of possible bioterrorism agents based on a number of criteria, including ease of obtaining and producing the agent, the agent’s stability in the environment, and whether the agent is contagious and/or lethal. Next, the CDC grouped the agents into three categories based on the likelihood of their use as a biological weapon. The categories are A, B and C, with Category A being the most likely agents to be used as an aerosolized agent. Category A agents are: anthrax, smallpox, botulism, viral hemorrhagic fever, tularemia and plague.

For all six of these agents, “Standard Precautions” in infection control are to be followed, including hand washing and wearing gloves, masks, eye protection and face shields.

Precautions include:

  • Wear gloves when touching blood, bodily fluids, secretions, excretions and contaminated items.

  • Put on clean gloves just before touching mucous membranes and non-intact skin.

  • Change gloves between tasks and procedures on the same patient after contact with material that may contain a high concentration of microorganisms.

  • Remove gloves promptly after use and before touching uncontaminated items and environmental surfaces

  • Wash hands immediately after removing gloves, between patient contacts and when otherwise indicated to avoid transfer of microorganisms to other patients or environments.

    ANTHRAX

    Anthrax is caused by Bacillus anthracis, a gram-positive, spore-forming bacterium. This bacterium is found in soil worldwide. Humans contract the disease from close contact with animals or animal products infected with the bacteria. Of the three routes of exposure – inhalation, cutaneous, and gastrointestinal – inhalation anthrax is of greatest concern as a bioweapon.1 Inhaled spores can germinate for up to 60 days in the mediastinal lymph nodes; therefore, the period between exposure and onset of symptoms may be as long as several weeks. Inhalation anthrax is the most lethal form, with mortality of 45% to 87% following inhalation of spores, and the most likely form of the disease to occur in a bioterrorism event.

    Diagnosis of inhalation anthrax is difficult, since there are no specific laboratory tests, but a widened mediastinum with or without infiltrates on chest x-ray is highly suggestive in a young or otherwise healthy person with the typical presentation. Bloody pleural effusions are also common. Basic diagnostic testing should include Gram stain and culture of blood, which can be obtained following your facility’s standard routine.

    Regardless of the form of the anthrax disease, Standard Precautions for infection control are recommended. Several sources recommend Contact Precautions for cutaneous anthrax for persons with draining lesions. Patients should be placed in a private room and gloves should be worn when entering the room and removed before leaving the room. Hands should be washed with an antimicrobial agent or a waterless hand-washing agent immediately after removing gloves. Gowns should also be worn when entering the room if it is anticipated that clothing will have contact with the patient, environmental surfaces, or items in the room. The gown should be removed before leaving the patient’s room.

    SMALLPOX

    Smallpox is the most devastating infectious disease in the history of mankind. It has killed over 500 million people worldwide. There are two forms of smallpox. Variola major is a severe and more common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox: Ordinary – the most frequent, accounting for 90% of all cases; Modified – a mild form occurring in persons previously vaccinated for smallpox; Flat – a very rare and fatal form; and Hemorrhagic – a very rare and very fatal form. Variola minor is a much less severe and less common form of smallpox, with death rates of 1% or less.

    Exposure to the virus is followed by an incubation period during which people do not have any symptoms and may feel fine. The incubation period averages about 12 to 14 days, with a range from 7 to 17 days. Typically, a two-stage illness will follow: the Prodrome stage, lasting from two to four days, including a fever in the range of 101 to 104 degrees Fahrenheit, followed by the Eruptive stage, the most contagious.

    Person-to-person transmission of smallpox occurs by aerosol droplets expelled from the oropharynx of infected persons, or by direct contact with an infected person. The virus can also be spread through contaminated bedding and clothing. Smallpox can also be spread through direct contact with infected bodily fluids. It is not known to be transmitted by insects or animals.

    Currently, there are no known effective antivirals. The discovery of a single suspected case of smallpox must be treated as an international health emergency and immediately brought to the attention of national officials through local and state health authorities. All contacts must be vaccinated within three to five days. Contacts include all household members, patients, staff, and visitors to the hospital at the same time as the smallpox case.2

    Standard Precautions of infection control are required with smallpox. Also, Contact Precautions include wearing gloves when entering the room; changing gloves after having contact with infectious material; removing gloves before leaving the room; and washing hands using an antimicrobial agent. Always place the patient in a private room. Airborne Precautions would also be necessary since the virus is spread through the aerosolized droplets expelled from the oropharnynx of infected patients. Some experts believe that home isolation would be the best alternative in a national emergency due to the high rate of nosocomial spread.

    BOTULISM

    Botulism is a rare but serious paralytic illness caused by a nerve toxin produced by the bacterium Clostridium botulinum, the most potent toxin known to humans. Of the seven antigenic types of C. botulinum (A-G), human botulism is caused mainly by types A, B, and E.

    The most common type of human botulism is acquired through the ingestion of toxin-contaminated food in which C. botulinum spores have germinated (gastrointestinal). Other routes of transmission include the inhalation of aerosolized toxin and germination in vivo in either a contaminated wound (wound botulism) or the gastrointestinal tract of infants (infant botulism).3 In the United States, an average of 110 cases of botulism are reported annually. Of these, 25% are food-borne, 72% infant, and 3% wound botulism. It is speculated that inhalation botulism would be the primary form of the disease if the botulism toxin were weaponized.4

    The incubation period is 12 to 72 hours, and botulism begins with the classic early non-specific “flu-like” symptoms including double or blurred vision, difficulty speaking, fatigue, and progressive muscle weakness. Death often results when the toxin attacks the respiratory system resulting in airway obstruction. Laboratory confirmation should be obtained from specimens of blood and stool to detect the toxin through bioassay testing. Treatment needs to be initiated as soon as diagnosis is suspected. Antitoxin, available from the CDC should be administered to all patients with known or suspected botulism. Antitoxin is made from horse serum and can produce very serious side effects including serum sickness and anaphylaxis. There is no person-to-person transfer of botulism; therefore, Standard Precautions are the only infection control measure necessary for these patients.

    HEMORRHAGIC FEVER VIRUSES

    Viral hemorrhagic fevers (VHFs) refer to a group of illnesses that are caused by several distinct families of viruses. Each disease causes a febrile syndrome characterized by hemorrhagic complications, but mortality rates, incubation periods, and susceptibility to antiviral therapy vary depending on the etiologic agent. While some types of hemorrhagic fever can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease. These organisms pose a biological threat due to their potential to cause severe morbidity, and because transmission can occur from person to person.5, 6

    The viruses that are considered the most dangerous if weaponized include the filoviruses (Ebola and Marburg), arenaviruses (Lassa fever, Junin, Machupo, Guanarito, Sabia), flaviviruses (Omsk hemorrhagic fever, Kyasanur Forest disease), and bunyaviruses (Rift Valley fever).

    Appropriate isolation precautions for patients with suspected or confirmed VHF include a combination of Airborne, Contact, Droplet, and Standard Precautions. Although airborne transmission of these agents appears to be rare, airborne transmission theoretically may occur; therefore, airborne precautions should be instituted for all patients with suspected VHF.

    Airborne Precautions include placing the patient in a private room with negative air-pressure ventilation, using external air exhaust or high-efficiency particulate air filters if the air is recirculated, and keeping the room’s door closed.

    Contact Precautions include placing the patient in a private room if available and wearing gloves when entering the room, changing gloves after having contact with infectious material, and removing gloves before leaving the room and washing hands using an antimicrobial agent.

    The following Personal Protective Equipment (PPE) for healthcare providers must be available: N-95 respirator or Powered Air-Purifying Respirator (PAPR); double gloves; impermeable gowns; face shields; goggles; leg and shoe coverings.

    Droplet Precautions include placing the patient in a private room or in a room with other patients who have the same infection. Healthcare workers should wear a standard surgical mask when working within three feet of the patient. Standard Precautions of infection control apply. In addition, all persons who have had close or high-risk contact with a patient suspected of having VHF during the 21 days following onset of symptoms should be under medical surveillance. If multiple patients with suspected VHF are admitted to one healthcare facility, group them in the same part of the hospital to minimize exposure to other patients and healthcare workers.

    TULAREMIA

    Tularemia is an acute infectious disease caused by Francisella tularensis. The organism is naturally occurring in a wide range of animal hosts, such as moles, mice, water rats, squirrels, rabbits, and hares, and can be recovered from contaminated water, soil, and vegetation. As few as ten organisms are sufficient to cause disease if inoculated into the skin or inhaled. Tularemia occurs naturally throughout much of North America, Europe, and Asia.

    F. tularensis could be used as a biological weapon in a number of ways, but the greatest concern would be focused on an aerosolized release that would cause pneumonic tularemia. Cases occurring in urban areas or in those with no risk factors should alert healthcare personnel to the possibility of a biological attack. Treatment of tularemia is critical to avoid progression to respiratory failure; meningitis; kidney, spleen, or liver involvement; sepsis; shock; and death.

    There is no rapid diagnostic testing available for tularemia. Physicians who suspect tularemia should collect specimens of respiratory secretions and blood. F. tularensis may be identified through direct examination of secretions, exudates, or biopsy specimens using Gram stain, direct fluorescent antibody, or immunohistochemical stains.

    Post-exposure prophylaxis with antibiotics should be initiated following confirmed or suspected bioterrorism exposure, and for post-exposure management of healthcare workers and others who had unprotected face-to-face contact with symptomatic patients. Person-to-person transmission of tularemia has not been documented; therefore, Standard Precautions in infection control are considered adequate for patients with tularemia.7

    There is a live attenuated vaccine commercially available for researchers with minimal adverse effects. There is no proven efficacy versus pneumonic tularemia.

    PLAGUE

    Plague is a disease caused by Yersinia pestis, a bacterium found in rodents and their fleas in many areas around the world. Under natural conditions, plague is transmitted to humans via rodent fleas infected with the bacterium, although humans can also contract it by direct contact with infected animal body tissues or by inhaling infected droplets.

    Of the three types of plague – bubonic, septic, and pneumonic – primary pneumonic plague is the most feared as a possible weaponized agent.8, 9 Yersinia pestis used in an aerosol attack could cause cases of the pneumonic form of plague. One to six days after becoming infected with the bacteria, victims would begin to develop the plague.9 At this time, the bacteria can spread to others who have had close contact with them. Because of the delay between being exposed to the bacteria and becoming sick, affected individuals could travel over a large area before becoming contagious and possibly infecting others. The mortality rate is almost 60% for treated patients, and 100% for untreated patients.

    There are no readily available rapid tests to detect plague. Physicians should obtain samples of blood, sputum, cerebrospinal fluid (CSF), and bubo fluid (if these exist). Definitive diagnosis is made by culture, which can be performed by the hospital laboratory. Plague is difficult to diagnose because it presents like regular pneumonia. If the patient is coughing up blood, consider plague.8

    Early treatment is extremely important, as mortality rates rise considerably if treatment is not initiated within 24 hours of symptom onset. Parenteral antibiotics will be given for at least 14 days.9

    There is no available vaccine in the U.S. since 1999. Research continues to develop new and improved plague vaccines, particularly in light of the current bioterrorist threat and concerns about intentional dissemination of aerosolized plague organisms.

    Droplet Precautions plus eye protection, in addition to Standard Precautions, should be implemented in infection control. Patients are considered infectious for 48 to 72 hours after initiation of appropriate antibiotic therapy with evidence of clinical improvement.8, 10 Contact Precautions should also be added to patients with the Bubonic form of Plague.

    Choosing a glove

    Informed use of personal protective equipment (PPE) is a critical component of a hospital’s infection control and bioterrorism response program. Appropriate PPE includes gloves, gowns, laboratory coats, face shields, masks, eye protection and ventilation devices. When choosing a glove, the first consideration should be the barrier requirement related to the procedure or task at hand. Be aware of the level of exposure risk that the patient-care activities will require.

    When selecting a medical glove, the two primary considerations should be barrier protection and allergen content. If a glove does not provide an intact barrier, it is not doing its job. To maximize barrier effectiveness, you may wish to choose a glove manufacturer that is reliable and experienced, so that your gloves will be of consistent quality and regularly available.

    Latex remains the gold standard for hand barrier protection due to its strength, proven barrier protection, elasticity, fit, feel, comfort and relatively low cost. Nitrile or neoprene gloves are recommended alternatives for those with latex allergies. Nitrile and latex examination gloves are comparable in barrier properties during in-use performance.11 Nitrile’s puncture resistance is far superior to that of latex, and it exhibits excellent resistance to most chemicals. Nitrile’s elasticity is very good, and the gloves tend to conform to the shape of the wearer’s hand, providing good comfort and fit.

    Many hospitals provide a latex-free material called polyvinyl chloride (PVC), commonly known as “vinyl,” as a choice for exam gloves. PVC is a petroleum-based film, but it is not molecularly cross-linked and is susceptible to small holes and breaches. Studies have shown that 63 percent of vinyl exam gloves permitted leakage of a test virus after normal use, compared with seven percent for latex exam gloves.11

    For surgical gloves, neoprene or copolymer provide excellent barriers, have no latex proteins, and are safe for those with latex allergies. Neoprene is a petroleum-based, cross-linked film that provides barrier protection similar to latex. A copolymer glove is a petroleum-based, cross-linked film that provides high strength, elasticity, comfort and barrier protection.

    REFERENCES

    1 Pile JC, Malone JD, Eitzen EM, Friedlander AM. Anthrax as a potential biological warfare agent. Arch Intern Med. 1998;158:429-34.

    2 Drugs and vaccines against biological weapons. Med Lett Drugs Ther. 1999;41:15-6.

    3 Shapiro RL, Hatheway C, Becher J, Swerdlow DL. Botulism surveillance and emergency response. JAMA 1997;278:433-5.

    4 U.S. Army Medical Research Institute of Infectious Diseases. Medical Management of Biological Casualties Handbook. Fort Detrick: USAMRIID; 1998.

    5 Infection Control for Viral Hemorrhagic Fevers in the African Healthcare Setting. CDC and WHO; 1998:1-198.

    6 Ebola: the virus and the disease. J Infect Dis. 1999;179(Suppl 1):S1-288.

    7 Centers for Disease Control and Prevention, the Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for isolation precautions in hospitals. Am J Infect Control 1996;24:24-52.

    8 DOD DFFUaE. NBC Domestic Preparedness Response Workbook. 1998.

    9 Franz D, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL, Bryne WR, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997;278:399-411.

    10. American Public Health Association. Control of Communicable Diseases in Man. Washington, DC: American Public Health Association; 1995.

    11. Korniewicz DM, El-Masri M, Broyles JM, Martin CD, O’Connell KP. Performance of latex and nonlatex medical examination gloves during simulated use. Am J Infect Control 2002;30(2):133-8.