REVIEW Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room B. A. Cunha Infectious Disease Division, Winthrop-University Hospital, Mineola and State University of New York School of Medicine, Stony Brook, New York, USA Bioterrorism has become a potential diagnostic consideration in infectious diseases. This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneu- monia, including laboratory and radiographic finding, are discussed. Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint. In addition to the clinical features of the infectious diseases mentioned, the artical discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents. The review concludes with suggestions for postexposure prophylaxis and therapy. Keywords Anthrax, Bioterrorism, Plague, Ebola, Smallpox, Tularemia, Zoonoses, Zoonotic/Atypical pneumonias Clin Microbiol Infect 2002; 8: 489–503 The emergency room is the most likely place tions early in an attack. The initial function of where victims of bioterrorism will first be encoun- physicians and consultants at the emergency room tered and evaluated. As we have learned from the level would be to identify sentinel cases involved anthrax experience in New York, mass casualties in the bioterrorism attack. It is critical to recognize are not necessarily to be expected. Even if large that a problem exists and will soon involve larger numbers of individuals are involved in a bioter- numbers of individuals. Aside from clinical recog- rorist attack, the initial cases will present as iso- nition of the signs and symptoms of agents related lated incidents or irregularly in low numbers. to bioterrorism, the emergency room has an Once an outbreak is identified, then it is relatively important infection control role. Infectious disease easy to disseminate information on the nature of clinicians will be essential to assist their emer- the infectious disease agent, in terms of its recog- gency room colleagues, and infection control per- nition and control. Emergency room personnel, sonnel will be needed to limit the spread of with the assistance of infectious disease clinicians, biological agents within the emergency room set- are the sentinels at the gate. ting to other patients as well as medical personnel. Biological agents for potential use in bioterror- Containment measures will be particularly impor- ism are many. Some are more readily available and tant with biological agents that are transmitted via easier to employ than are others. The most likely the airborne route, or by person-to-person contact. agents to be involved in bioterrorism attacks Finally, general supportive measures and specific include Bacillus anthracis, Yersinia pestis, Clostri- antimicrobial therapy, antitoxins or vaccines will dium botulinum, Francisella tularensis, and possibly be needed to treat the affected patients, and this the viral agents of African hemorrhagic fevers. The treatment will begin in the emergency room. emergency room, as the initial point of contact for Emergency room personnel will need the early most bioterrorism victims, has three critical func- and substantial support of specialists related to the problems encountered with the various bioterror- Corresponding author and reprint requests: B. A. Cunha, ist agents. Infectious disease consultants will be Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA critical in the evaluation of all potential or real Tel: þ1 516 663 2505 bioterrorist cases. Infection control, as mentioned Fax: þ1 516 663 2753 previously, will be essential in containing the ß 2002 Copyright by the European Society of Clinical Microbiology and Infectious Diseases 490 Clinical Microbiology and Infection, Volume 8 Number 8, 2002 infection where appropriate, to prevent loss by advised to rule out other neurologic conditions illness of critical medical personnel during an with similar features. Respiratory paralysis may outbreak. Physicians with experience in toxin- occur in severe cases. Importantly, mental status is mediated diseases will also be needed if these unaffected by botulism; no signs of encephalitis or agents are employed in a bioterrorism attack. encephalopathy are present, and nuchal rigidity is On-going supportive care will be needed in the not present, i.e. there is no evidence of meningitis. management phase for those severely affected by The incubation period is 10–12 h, but this will not the attack. The emergency room also requires be helpful in the initial evaluation of the patient. intensive support from the microbiology labora- The incubation period is inversely proportional to tory, and must be in communication with autho- the quantity of toxin ingested. Some patients may rities to alert others of potential or actual threats have profuse vomiting without diarrhea. Differ- from biological weapons [1–8]. ential diagnostic possibilities include bulbar palsy, Guillain–Barre syndrome, or polio, but these con- BIOLOGICAL WEAPONS ditions do not closely resemble botulism. Guillain– TRANSMITTED BY FOOD OR WATER Barre syndrome is usually accompanied by some degree of fever, has a sensory component, and Clostridium botulinum characteristically begins as ascending rather than C. botulinum is a spore-forming organism that descending paralysis. Diagnosis of botulism is produces a potent exotoxin. The exotoxin is ther- confirmed by detecting botulism toxin in the stool molabile, but is extremely potent. Minute or serum [9–13]. amounts, if properly dispersed and disseminated, would be sufficient to eliminate the entire human population. Highly purified botulism toxin is Enteropathogens stable, easily transportable, and readily dispersed. Toxigenic or enteropathogenic Escherichia coli, Sal- Ideal vehicles for the transmission of the toxin monella or Vibrio cholerae are potential biological would be water supplies and selected food items, weapons. Such agents would have to be intro- but fortunately, such transmission is difficult to duced into water supplies in large numbers to achieve. Food-borne botulism requires the intro- be recognized as biological weapons. At any given duction of the toxin into foods at the level of the time, there are sufficient sporadic cases of poorly packing plant. This would require terrorists using characterized febrile diarrheal illnesses in the this biological agent to have access to such a population to make the detection of these agents facility. In contrast, water-borne botulism toxin difficult. Only if they occurred in large num- would be much easier to use, but because of bers, suggesting an outbreak, could the possibility difficulties with dispersal of the toxin in large of bioterrorist be entertained. Clinicians are famil- volumes of water, it would be difficult to utilize. iar with the clinical presentation of these infecti- Botulism toxin could be easily placed in reservoirs ous diseases and they are rarely fatal. The use or water tanks, but would not mix completely or of enteropathogens as biological weapons would evenly in the target volume of water. Therefore, create anxiety and cause some illness, but water-borne botulism is likely to occur as sporadic would be minimally disruptive to society. When attacks, since it is unlikely that large numbers of these infectious diseases are not self-limited, people would be affected simultaneously, due to they are readily treatable with antimicrobial the difficulties in dispersing the toxin in large agents [4–6]. volumes of water. In the emergency room, botu- lism will present as descending symmetric paraly- BIOLOGICAL WEAPONS sis, starting with cranial nerve involvement. Onset TRANSMITTED BY CONTACT would be heralded by the presence of blurry vision, which is rapidly followed by ocular muscle Ebola/viral hemorrhagic fevers paralysis, difficulty in speaking, and/or the inabil- Person-to-person transmission is a potential way ity to swallow. Fever is not a feature of botulism, to spread some bioterrorist agents, particularly since it is a toxin-mediated disorder. There are few pneumonic plague and agents of African hemor- other conditions that could be confused with botu- rhagic fevers. These agents are highly contagious lism clinically, but neurologic consultation is and difficult to handle, and because of this are not ß 2002 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 8, 489–503 Cunha Bioterrorism in the emergency room 491 likely to be utilized as biological weapons. Ebola develop a camelback fever curve, and a pulse fever, Rift Valley fever, etc. could be transmitted temperature deficit (relative bradycardia). Ebola by a terrorist willing to be infected by these agents. and related hemorrhagic fevers are often accom- The terrorist would have to travel to the intended panied by leukopenia, lymphopenia, and throm- area during the incubation period of the infection bocytopenia; these are important laboratory clues in order to initiate person-to-person transmission, to help the clinician differentiate these illnesses by secretion contact and/or, to a lesser extent, by from sporadic cases of gastroenteritis in the com- airborne dissemination. Ebola fever begins