Epidemiology Newsletter
Office of Epidemiology October 2001 Utah Department of Health
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Bioterrorism: Background and High Priority Agents

People have been using bioterrorism to do horrible things to each other since time began. For several years, many have questioned when the next bioterrorism event would occur, rather than if it would occur. While that question has been answered in recent weeks, we do not know how far-reaching the effects might become.

Terrorism is a form of psychological warfare causing fear among the public, in addition, to casualties. Bioterrorists have achieved that objective nationwide with plenty of reverberations in Utah. Utah law enforcement officials have deemed more than 130 incidents as suspicious enough to warrant further investigation and testing from October 11 through October 31, 2001. In that time, the Utah Department of Health (UDOH) has not detected B. anthracis spores in any environmental or clinical sample submitted for testing. Unfortunately, that is not the case on the East Coast as anthrax cases continue to surface. As of October 31, 2001, four deaths have resulted from inhalational anthrax, including one Florida resident, one New York resident, and two Washington D.C. postal workers. Five additional inhalational anthrax cases have been identified, including another Florida resident, one New Jersey Postal worker, two additional Washington D.C. postal workers, and one mail handler from the State Department offsite mailroom. In addition, three cases of cutaneous anthrax have been identified in both New York and New Jersey. Environmental sampling and testing have revealed anthrax spore contamination in postal facilities, media organizations, and government buildings located in Florida, Maryland, New Jersey, New York, Virginia, and Washington D.C.

The proper response to these findings continues to be defined and clarified while preventative efforts continue to be implemented. While vaccination has been the single most cost-effective public health intervention in history, it is impractical to stockpile or administer vaccines sufficient to protect every citizen from every biological agent. The very high costs and the great difficulties involved in vaccinating large populations, along with the broad spectrum of potential agents, make it impossible to use vaccines to protect the general population against bioterrorism. Thus, vaccines cannot be considered a first line of defense against bioterrorism for the general population, as they can be for the relatively small military population. What is practical is a strategy to detect an event as early as possible, respond quickly, and deliver resources efficiently. Health officials need to maintain a high level of suspicion and improve surveillance capacity. The foundation of a good disease surveillance system is a framework of physicians, physician assistants, nurse practitioners, and clinical laboratorians who will recognize the public health implications of reportable diseases, disease clusters, unusual illnesses, and who will notify health department officials so that public health action can be undertaken promptly and efficiently.

The UDOH would like to remind providers to be especially vigilant, not only for symptoms consistent with anthrax, but also for symptoms consistent with other potential bioterrorism agents. Although nearly any microbe could be put to criminal use, the Centers for Disease Control and Prevention has classified six diseases as “Category A,” or high priority disease, because they 1) can be easily disseminated or transmitted person to person; 2) cause high mortality, with potential for major public health impact; 3) might cause public panic and social disruption; 4) and require special action for public health contingency planning. Figure 1 includes Category A diseases, suspicion of any of which should prompt an immediate call to the local or state health department.

Figure 1. Epidemiology and Microbiology of Category A Bioterrorism Agents

Disease/Microbiology

Diagnostic Notes

Anthrax, Bacillus anthracis, a spore-forming Gram-positive rod Inhalational anthrax is the most lethal form of anthrax. The incubation period typically ranges from 1 to 7 days but may last up to 60 days. Initial symptoms include mild fever, muscle aches, and malaise. Inhalational anthrax has a high case-fatality rate, progressing to respiratory failure (with radiographic evidence of mediastinal widening) and shock. Cutaneous anthrax is the most common form of the disease and appears to require lower doses of spores rubbed into the skin or introduced into cuts in the skin. The incubation period ranges from 1 to 12 days. A skin lesion evolving from a papule, through a vesicular stage, to a depressed black eschar, characterizes cutaneous anthrax. The lesion is usually painless, but patients may also have fever, malaise, headache, and regional lymphadenopathy. (Note: Recent cutaneous anthrax cases had lesions clinically identified as “Brown Recluse bites”). Gastrointestinal anthrax usually follows after eating raw or undercooked contaminated meat and can have an incubation period of 1 to 7 days. Symptoms are severe abdominal pain followed by fever and signs of septicemia. Lower bowel inflammation typically causes nausea, loss of appetite, and fever followed by abdominal pain, hematemesis, and bloody diarrhea.
Botulism, neurotoxins produced by the anaerobic Gram-positive rod Clostridium botulinum The botulinum toxins are the most toxic compounds, per weight of agent, known to man, requiring only 0.001 microgram per kilogram of body weight to kill 50 percent of animals studied. Botulism usually begins with cranial nerve palsies, including ptosis, blurred vision, diplopia, dry mouth and throat, dysphagia, and dysphonia. This is followed by symmetrical descending flaccid paralysis, with generalized weakness and progression to respiratory failure. Symptoms generally begin as early as 12 to 36 hours after inhalation or ingestion of spores.
Plague, Yersinia pestis, a Gram-negative rod Clinical features of pneumonic plague include fever, cough with muco-purulent sputum, hemoptysis, and chest pain. A chest radiograph will show evidence of bronchopneumonia. The incubation period is 1-7 days. Early administration of antibiotics is critical as pneumonic plague is invariably fatal if proper therapy is delayed more than one day after the onset of symptoms.
Smallpox, Variola virus, an orthopoxvirus If one inhales a single particle of smallpox, he or she can come down with the disease from 7-19 days. The acute clinical symptoms of smallpox closely resemble other acute viral illnesses. In order for prompt public health intervention to take place, smallpox must be distinguished from other vesicular exanthems, such as chickenpox, erythema multiforme with bullae, or allergic contact dermatitis. Smallpox begins with a 2- to 4-day nonspecific prodrome of fever and myalgias before rash onset. Of particular importance is that clinicians differentiate varicella (chickenpox) from smallpox. The rash of varicella is most prominent on the trunk and develops in successive groups of lesions over several days, resulting in lesions in various stages of development and resolution. In comparison, the vesicular/pustular rash of smallpox is typically most prominent on the face and extremities, and lesions develop synchronously. (Note: most people vaccinated for smallpox have had a waning immunity after 10 years.)
Tularemia, Francisella tularensis, a Gram-negative rod Inhalation of only a few F. tularensis organisms can cause an abrupt onset of an acute, nonspecific febrile illness beginning 3 to 5 days after exposure, with pleuropneumonitis developing in a substantial proportion of cases during subsequent days. Pneumonic tularemia is a severe atypical pneumonia that may be fulminant and with a high case fatality rate if left untreated.
Hemorrhagic fever, Ebola and Marburg, filoviruses Characterized by abrupt onset of fever, myalgia, and headache with an onset of 2-19 days following exposure to body fluid of infected person. Other signs and symptoms include nausea and vomiting, abdominal pain, diarrhea, chest pain, cough, and pharyngitis. A maculopapular rash, prominent on the trunk, develops in most patients approximately 5 days after onset of illness. Bleeding manifestations, such as petechiae, ecchymoses, and hemorrhages, occur as the disease progresses.

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Bioterrorism: Responding Step by Step

Monday 4:00 a.m.
The pager goes off. A seasoned epidemiologist awakens to find an odd number displayed. The call is immediately returned to hear the voice of a concerned and anxious first responder. The responder inquires about how to handle a potential infectious substance and what protocols to follow. Instruction is given by the epidemiologist and coordination is in place to ship the sample to the state lab for analysis. Consultation is provided concerning steps to protect the first responders and others possibly exposed. A call is made by the epidemiologist to a public health microbiologist who travels to the laboratory and is awaiting the sample when it arrives. Tests are initiated to discover the identity of the substance.

Thursday 3:30 p.m., Three Days Later
A call is received from a local hospital notifying public health that they have seen an unusual increase in patients presenting with clinical symptoms that suggest an infectious disease outbreak (for example, patients presenting with an unexplained febrile illness associated with sepsis, pneumonia, adult respiratory distress, and mediastinitis). Laboratory work is again sent to the state laboratory for testing. A presumptive diagnosis is made by the physician along with input from public health. Appropriate precautions and possible treatments are discussed with the physician.

Thursday 5:30 p.m.
A team of epidemiologists are sent to the hospital to begin an epidemiological investigation to discover the source of exposure and to see if the sample provided by first responders earlier in the week could be linked to the hospitalized individuals. The investigators’ goal is to identify and characterize the cluster of illness and identify the potential public health impact.

As the epidemiologists complete the initial steps of the investigation, it appears this could be a bioterrorism event. Public health contacts local law enforcement and the Federal Bureau of Investigation. Appropriate information is shared with these agencies and the choice is made to conduct further joint interviews.

A call is made by the state epidemiologist to the Centers for Disease Control and Prevention (CDC). The CDC sends additional personnel to assist with the investigation.

Thursday 6:00 p.m.
The state health department sends notification via the Health Alert Network (HAN) to all state health departments, other hospitals and various other state agencies notifying them of the situation and initial investigation results. A message is delivered to recipients of the state’s infectious disease list server in attempt to notify and explain what is being seen.

Friday Morning
Presumptive tests are completed by the state lab. Public health recommends appropriate control measures, treatment and prophylaxis guidelines for what presumptively is a life-threatening illness. Again, both the HAN and list server send out additional findings to all recipients.

Public health begins to notify the medical community more extensively to discuss findings and to coordinate treatment protocols.

The public information officer from the health department issues a press release to notify the public of these findings and to recommend any needed action to be taken.

Friday 3:00 p.m.
Many physicians and hospitals are also reporting numerous cases of related illnesses that they have seen within the past 24 to 48 hours. Public health contacts local pharmaceutical distribution centers to request additional supplies of medication.

State public health officials, in consultation with the CDC, request the National Pharmaceutical Stockpile.

The public information officer and other officials hold a press conference to update the media and public and recommend actions to be taken.

Saturday
Public health is distributing pharmaceuticals to potentially exposed individuals and medical supplies where needed.

Public health and the American Red Cross are coordinating certain areas of response including prophylaxis centers, psychological treatment personnel and pastoral services, as well as additional medical response resources and personnel.

Epidemiologists continue gathering case counts/information and related statistics. Data management, disease tracking, coordination with the medical community, public education and implementation of control measures are continuing and will continue throughout the event.

Conclusion
There is a tendency for terrorists to move into new areas of violence when current areas no longer achieve the intended effect – publicity, reaction, chaos. As terrorism creeps into the biological realm, the greatest payoff in combating it lies in focusing on how best to respond to an attack. A coordinated effort within organizations and between public health, emergency responders, the medical community and other response agencies is needed to effectively and efficiently respond to a bioterrorism event. Public health needs to continue to plan and acquire resources to respond to such events, while the medical and emergency service communities need to ensure that they are trained to recognize the symptoms of diseases associated with bioterrorism agents.

We are today with respect to bioterrorism where we were nearly 30 years ago with respect to “conventional” terrorism. A new international threat was emerging then, but it was unclear as to the direction it would take. It took years to comprehend the diverse nature of those kinds of events (highjackings, hostage situations, bombings) and for governments to take actions against them. Biological terrorism does not give us the luxury to watch events unfold and then determine the proper resources. As bioterrorism events could have catastrophic effects in terms of lives lost and create a medical, political, and social crisis unparalleled in our history, it is important to prepare now for this new age of terrorism.

Join the List Server
If you are interested in joining the Utah Infectious Disease List Server, please email Jenifer Lloyd at jlloyd@utah.gov.

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Anthrax Facts: Test Your Knowledge

1. Fact or fiction: More than 95% of anthrax cases are inhalational.

Fiction ! Ninety-five percent of anthrax cases are cutaneous cases. Before October 2001, no case of inhalational anthrax had been reported in the United States since 1978.

2. Fact or fiction: A nasal swab test is not an approved diagnostic tool for determining whether or not a person has been exposed to anthrax.

Fact ! At present, the Centers for Disease Control and Prevention does not recommend the use of nasal swab testing on a routine basis to determine whether a person has been exposed to B. anthracis or as a diagnostic tool. At best, a positive result may be interpreted only to indicate exposure, whereas, a negative result does not exclude the possibility of exposure. Nasal swabs are discouraged except in situations where a positive powder was identified. Public health officials may use nasal swab screening to evaluate the dispersion of spores.

3. Fact or fiction: Household contacts of anthrax cases should be given antibiotic prophylaxis.

Fiction ! Since anthrax is not transmissible person to person, there is no need to quarantine people suspected of being exposed to B. anthracis or to treat contacts (e.g., household contacts, friends, or coworkers) of people ill with anthrax, unless the contacts were also exposed to the same source of infection.

4. Fact or fiction: Patients reporting flu-like illness should be tested for anthrax.

Fiction ! There is very little reason to suspect anthrax unless a patient has had a specific exposure. To cause infection, B. anthracis spores must enter the skin, be ingested, or inhaled (infection results from inhalation of 8,000- 40,000 bacterial spores). If anthrax is suspected, the diagnosis can be confirmed by obtaining the following appropriate laboratory specimens based on the clinical form of anthrax:

  • Inhalational: blood, CSF, and/or sputum

  • Cutaneous: vesicular fluid and/or blood

  • Gastrointestinal: vomitus, feces, and/or blood

5. Fact or fiction: Anthrax infection is curable if treated early.

Fact ! Although effectiveness may be limited after symptoms are present, high dose antibiotic treatment should be undertaken. Supportive therapy may be necessary. The case fatality rate for inhalational anthrax approaches 100% unless antibiotic treatment is initiated before disease onset. Prophylactic treatment is very effective if begun promptly following an exposure. The case fatality rate for cutaneous anthrax is 20% without, and <1% with, antibiotic treatment. The case-fatality rate for gastrointestinal anthrax is estimated to be 25 to 60%, and the effect of early antibiotic treatment is not established.

Treatment options: The current B. anthracis strains associated with the intentional exposures are susceptible to ciprofloxacin and doxycycline. The current strains are also susceptible to chloramphenicol, clindamycin, rifampin, vancomycin and clarithromycin, but there are limited or no data on the effectiveness of using these agents for B. anthracis infections or exposures. Cephalosporins should not be used for post-exposure prophylaxis or treatment of B. anthracis infections. Amoxicillin or penicillin VK may be an option for post-exposure prophylaxis in situations where ciprofloxacin or doxycycline is contraindicated. Combination therapy with two or more antimicrobials may be appropriate in patients with severe infections.

To view an interactive tutorial to learn additional anthrax facts please visit the following webpage: http://www.nlm.nih.gov/medlineplus/tutorials/anthrax.html

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Utah Department of Health, Office of Epidemiology
Monthly Morbidity Summary - October 2001 - Provisional Data

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The Epidemiology Newsletter is published monthly by the Utah Department of Health, Division of Epidemiology and Laboratory Services, Office of Epidemiology, to disseminate epidemiologic information to the health care professional and the general public.

Send comments to:  The Office of Epidemiology, Box 142104, Salt Lake City, UT 84114-2104, or call (801) 538-6191

Approval 8000008:  Appropriation 3705

Rod Betit, Executive Director, Utah Department of Health
Charles Brokopp, Dr.P.H., Division of Epidemiology and Laboratory Services
Gerrie Dowdle, MSPH, Managing Editor
Connie Dean, Production Assistant

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