What the acute care physician needs to know about bioterrorism

While it seems unlikely that acts of bioterrorism would occur in Canada, bioterrorist attacks are of great concern in the United States (1–3). It is almost inconceivable that an event in the United States would not have some impact in Canada, given the frequency of international travel. Just as a resident of the greater Toronto area fell victim to West Nile Virus encephalitis following a visit to New York, New York during the 1999 summer epidemic, and hundreds of travellers returning to Canada develop malaria each year, infected travellers could return to Canada while in the incubation stage of an infection resulting from bioterrorism. Furthermore, diseases that are communicable by person-to-person contact, such as smallpox and pneumonic plague, can cause secondary cases that are in the incubation stage before the index case is recognized.

While it is hoped that physicians in Canada will never face a crisis that would require the information presented in this paper, it behooves all involved in acute care to familiarize ourselves with the potential reality of bioterrorism and its management. A plan of action must be formulated and put in place before such a situation occurs – if it ever does occur. Unlike warfare, the target of the bioterrorist is the civilian population. Acute care staff needs to be able to diagnose diseases that are most likely the result of microbial bioterrorism. There must be a plan of medical management in place in the health care setting to ensure that preventive action, such as a quarantine, and the immediate and orderly distribution of vaccines and antimicrobial drugs, can be taken to minimize disease transmission. Colleagues who work in public health, laboratories, infection control and occupational health are vital partners in medical management, together with emergency services response groups (eg, police, ambulance, city authorities) and criminal investigation units.

THE STATUS OF BIOTERRORISM

The antibiological terrorism agreement of 1972, the Biological Weapons and Toxins Convention, has not been adhered to by important cosignatories (1). At least 17 nations are believed to have biological weapons programs with offensive capabilities (4), as do some autonomous terrorist groups (1). Biotechnology has advanced to the degree that certain organisms can be readily produced and efficiently aerosolized in crowded structures such as airports and shopping malls. The new millennium may have special significance to terrorist groups and to individuals capable of such atrocities. Although smallpox was considered to be eradicated from the world in 1978, inspection teams from the United Nations have expressed concern regarding the disposition of large stores of the smallpox virus after the closure of bioweapons facilities in the former Soviet Union (5). The implications are frightening if microbial agents had been used instead of bombs in recent events, such as the bombings of the World Trade Center in New York City, the Federal Building in Oklahoma City, Oklahoma, Centennial Olympic Park, Atlanta, Georgia, and the American embassies in Tanzania and Kenya (3). The unavoidable delay in diagnosis during an incubation period would most likely have an impact beyond the contamination site itself if the causative organism is transmissible by person-to-person contact or if the victim travels.

It must be remembered that terrorism involving biological agents can easily be mistaken for naturally occurring outbreaks until a thorough scientific investigation is completed. Conversely, examples of naturally occurring events that might initially have been mistaken for bioterrorist acts include the Legionnaires’ disease outbreak in Philadelphia, Pennsylvania in 1976 and the occurrence of hantavirus pulmonary syndrome in the Southwest United States in 1993 (3). The deliberate contamination of food products has been reported in a hospital laboratory (6) and in a community (7). In the latter incident, 751 cases of Salmonella typhimurium infection from salad bar contamination were traced to followers of Bhagwan Shree Rajneesh who were endeavouring to influence a local election in the United States.

Leadership in addressing the above issues is being provided in the United States by the Working Group on Civilian Biodefense. The Working Group’s membership includes the United States Army Medical Research Institute of Infectious Diseases (USAMRID), the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, The Johns Hopkins University, Baltimore, Maryland and internationally recognized leaders in infectious diseases and epidemiology. The Working Group’s statements on anthrax and smallpox have been published in The Journal of the American Medical Association (1,2). Symposia about bioterrorism are regularly held within the infectious diseases community.

WHICH DISEASES MAY APPEAR?

Clinicians in acute care settings should be familiar with the clinical manifestations, diagnostic techniques, isolation precautions and chemotherapy and/or chemoprophylaxis of smallpox, pneumonic plague, viral hemorrhagic fevers and anthrax. The first three microorganisms may be transmitted via person-to-person contact either directly or via vectors (eg, mosquitoes) naturally or with minimal chemical alteration. A number of other microorganisms have also been recognized for their bioterrorist potential (3). Illnesses that might result from bioterrorism could present as a papulopustular rash on the extremities (smallpox) (2), hemorrhagic mediastinitis (anthrax) (1,8), and hemorrhagic pneumonia (pneumonic plague), as well as encephalitis, hemorrhagic fever or enteric diseases. However, the initial symptoms of many of these diseases (ie, fever, ‘influenza-like’ symptoms) are nonspecific, and the early stages of a disease may go unrecognized. The intentional use of an infectious agent may be further suspected with a history of travel (eg, to the United States or elsewhere) in the presence of a rare or previously nonendemic disease, or in an epidemic situation. In summary, the following should be noted.

Smallpox

After a seven- to 17-day incubation period, a patient with smallpox (2) experiences a high fever, malaise, prostration, headache and backache. Three to four days after symptoms first appear, a maculopapular rash appears on the mucosa of the mouth and pharynx, face and forearms, and spreads to the trunk and legs. In contrast to varicella, the highest concentration of lesions is on the extremities. Within one to two days, the lesions become vesicular, then pustular, with crusting beginning on day 8 or 9. Transmission occurs only in the presence of a rash. The diagnosis of a single case would constitute an international health emergency.

Inhalational anthrax

The incubation period for inhalational anthrax (1,8) is two days to approximately two months. Epidemiologically, its appearance would be suggested by the sudden occurrence of multiple cases of severe influenza-like illness with a fulminant course and an 80% mortality rate; half of the mortalities occur within the first 24 to 48 h of illness. Chest radiographs will show mediastinal widening, and a peripheral blood smear may show Gram-positive bacteria. The preliminary identification on blood culture at 6 to 24 h would be Bacillus species. While penicillin and tetracycline should be effective, the possibility of genetically engineered resistance may necessitate the use of the quinolone antibiotics. Ciprofloxacin for 60 days is the current empirical treatment of choice, regardless of the recipient’s age. There is no documented person-to-person transmission.

Pneumonic plague

Pneumonic plague, the so-called ‘Black Death’, may be heralded by reports of excessive deaths of rodents, which were bitten by infected fleas. It is characterized by a fever, cough, hemoptysis, bilateral pneumonic infiltrates and rapid death, as well as acral necrosis of the digits or nose. Parenteral aminoglycoside therapy is the treatment of choice, although oral doxycycline, tetracycline, quinolones or chloramphenicol may be effective. Person-to-person transmission can occur.

Viral hemorrhagic fevers

Arboviral infections may cause a sporadic central nervous system infection (eg, encephalitis, aseptic meningitis, commonly with seizures), and undifferentiated febrile illness, fever with rash, hemorrhagic manifestations, hepatitis, myalgia or polyarthritis.

WHAT PREVENTIVE ACTION SHOULD BE TAKEN?

Physicians need to be aware of the potential for bioterrorism and to have knowledge of the most likely causal agents. Public health authorities must have an adequately trained and equipped response team at local, provincial, territorial and federal levels. This includes a process to provide access to and distribution of appropriate vaccines and antimicrobial drugs.

Establishment of a definitive diagnosis in an infected patient and notification of infection control and public health authorities is an essential first step of controlling an outbreak. Currently, there are very few laboratories equipped and trained to identify any of the likely causal agents. The impact of smallpox can be drastically reduced by the use of vaccine, although vaccine-associated morbidity and mortality after primary immunization is considerable (9). Vaccination within four days of exposure offers significant protection against a fatal outcome. However, at this time, vaccine supplies in the United States are very limited and of unknown efficacy. Pregnant women, immunocompromised patients and possibly others would ideally require concomitant administration of vaccinia immune globulin. Immunity to primary immunization is unlikely to extend beyond 27 years based on antibody studies indicating that most persons vaccinated at birth would most likely be susceptible. Preventive vaccine for anthrax, currently only available to the military, is administered as a six-dose series. Postexposure antibiotic prophylaxis is identical to the therapeutic regimen provided above.

The threat of bioterrorism has long been with us. This threat was the impetus for the establishment of the Epidemic Intelligence Service in 1951, now a routine part of CDC activity in the United States (3). Just as plans exist for rare catastrophic events such as fires and ice storms, so must society plan to deal with a bioterrorist attack. Because of diseases such as smallpox and pneumonic plague, with attack rates of essentially 100% and fatality rates of 20% to 35%, our civilization would experience major alterations in the availability of food supplies, health care delivery, the functioning of financial markets and the availability of expertise. Any international and professional initiatives analogous to Physicians for Social Responsibility, an organization that provides education on nuclear destruction, which would alert society to the unparalleled destruction of bioterrorism should be encouraged. There are useful websites on bioterrorism preparedness and other bioterrorism-related information, including The Johns Hopkins site <www.hopkins-biodefense.org>, the CDC site <www.bt.cdc.gov> and the Planned Response Exercises and Emergency Medical Preparedness Training site <Home.eznet.net/~kenberry>.

The impact of a bioterrorist attack or even the threat of an attack goes far beyond the actual morbidity and mortality caused by the agents that may be used. Widespread panic, overwhelmed hospital resources and disruption of social services would occur. Unlike other weapons of mass destruction, biological agents continue to wreck havoc with secondary and tertiary transmission and sequelae in geographically diverse regions months after the initial attack. Unless we have the courage to consider the possibility, we cannot ensure that plans will be in place to protect the public and minimize the consequences of bioterrorism (10). In the words of Donna Shalala, United States Secretary, Department of Health and Human Services: “The fight against bioterrorism must be a global fight. We must not be afraid, but we must be aware.” A coordinated provincial, territorial and federal preparedness plan to help combat potential threats to the Canadian public is urgently needed.