Journal meeting

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Journal meeting

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• Date 91 07 06

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Bioterrorism Preparedness What Practitioners
Need to Know

• Infections Medicine 497-515 2001

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Introduction

• A premeditated biologic attack against a civilian
  population is now a real threat.
• Terrorist organization or individual may employ
  biologic agents for less "ambitious" reasons to
  cause social or political disruption, or simply
  to generate fear and mistrust

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Introduction

• Despite the ban 1972 Biological and Toxin
  Weapons Convention, signed by more than 140
  countries
• The facts remain that lethal and highly noxious
  biologic agents are relatively inexpensive, are
  easy to obtain

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Purposes

• This article are to address the needs of
  infectious disease specialists and other health
  care practitioners as they are forced to confront
  this problem
• Familiarity with these agents and their
  associated diseases may help physicians recognize
  the possibility of a deliberate attack and manage
  the consequences

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Why the concern?

• North Korea, Syria, Iraq, and Iran
• Massive biologic weapons development in Russia
  beginning in the early 1970s
• 1992 Ebola fever outbreak, in an attempt to
  obtain Ebola virus samples for cultivation and
  weapon development

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Biologic Weapons and Associated Disease

• Anthrax
• Plague
• Tularemia
• Smallpox
• Staphylococcal Enterotoxin B

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Anthrax

• September-October 2001 anthrax bioterrorism
  events in the United States
• Caused by B anthracis, a gram-positive,
  spore-forming bacillus (zoonotic disease )
• Cutaneous, GI, and inhalational

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Anthrax

• 95 of naturally occurring anthrax cases are
  cutaneous
• Little clinical experience with the inhalational
  form of this disease (it is the form most likely
  to result from intentional delivery of this agent
  via aerosol )

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Inhalational anthrax

• Incubation period of 1 to 6 days
• Nonspecific prodromal flu-like phase that
  features fever, headache, nausea, malaise, and
  fatigue a nonproductive cough, dyspnea, and a
  sensation of substernal oppression may be present
  

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Inhalational anthrax

• followed by rapid development severe respiratory
  distress with
• dyspnea, diaphoresis
• stridor, cyanosis, and shock.
• Described primarily as a hemorrhagic, necrotizing
  mediastinitis and lymphadenitis

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Inhalational anthrax

• The chest x-ray film often reveals a widened
  mediastinum as well as pleural effusion.
• Meningitis is present in approximately half of
  cases
• Bacteremia, septic shock, and death typically
  follow in 24 to 36 hours

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• Mediastinal widening in chest radiograph from a
  patient with inhalational anthrax.

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Dignosis of anthrax

• Clinical laboratories should be notified of the
  suspicion of anthrax, since Bacillus isolates
  from blood cultures are not always speciated.
• Suspicion of inhalational anthrax, based on rapid
  progression of a flu-like illness to shock and
  death, accompanied by a widened mediastinum,
  should prompt immediate notification of the state
  health department.
• Enzyme-linked immunosorbent assay (ELISA) and
  polymerase chain reaction (PCR) assay for anthrax
  are available from national reference
  laboratories

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• Stained Bacillus anthracis

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Treatment of anthrax

• Fluoroquinolones and doxycycline for 60 days.
• The vaccine most recently licensed in the United
  States is a cell-free preparation of protective
  antigen
• A 6-dose course is recommended, although 3 doses
  may confer substantial protection

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Plague

• Yersinia pestis, a gram-negative bacillus
• Rodents are the primary reservoir
• Bubonic, pneumonic, or primary septicemic disease
• Pneumonic plague in humans follows an incubation
  period of 1 to 6 (usually 2 to 3) days and is
  characterized by acute onset of malaise high
  fever chills and cough, with initially watery
  and then bloody sputum.

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Plague

• Chest x-ray films reveal patchy or consolidated
  infiltrates.
• The disease progresses rapidly, producing
  dyspnea, stridor, cyanosis, and septic shock,
  resembling other fulminant pneumonias.
• The time from clinical onset to death is usually
  4 to 5 days.

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Treatment of Plague

• Streptomycin, gentamicin, tetracycline,
  fluoroquinolones, and chloramphenicol may be
  effective if begun early in the course of illness
  (less than 24 hours after onset of symptoms

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Tularemia(???)

• Francisella tularensis is a aerobic gram-negative
  coccobacillus
• Transmitted to humans from infected rabbits and
  other small animals via ticks, fleas, or deer
  flies or by direct contact

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Tularemia(???)

• The most common presentations are ulceroglandular
  and typhoidal disease
• An elevated creatine phosphokinase level,
  myoglobinuria, renal failure, and adult
  respiratory distress syndrome may complicate the
  course of tularemia.

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Tularemia(???)

• The diagnosis of tularemia is usually made by
  using serologic methods (ELISA) at least several
  weeks after the onset of illness
• Streptomycin is the drug of choice and gentamicin
  is an effective alternative
• Approximately 35 of untreated patients die of
  this disease

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Smallpox

• The last naturally occurring case of smallpox was
  reported in Somalia in October 1977
• This virus is extremely infectious by aerosol
  route
• Incubation period of 12 to 14 days (range, 7 to
  17 days),

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Smallpox

• Smallpox begin abruptly with fever, malaise,
  rigors, vomiting, headache, and backache
• After 2 to 3 days, a maculopapular eruption
  appears on the face, hands, forearms, and
  oropharyngeal mucosa
• 8 to 14 days after onset of the illness,
  formation of pigmented depressed scars

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Smallpox

• The most recent outbreaks of variola major
  carried mortality rates of 30 in nonimmunized
  persons and 3 in immunized persons
• Suspected placed in strict quarantine with
  respiratory isolation for 17 days
• PCR and ELISA are the most useful assays

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Staphylococcal Enterotoxin B Intoxication

• Staphylococcal enterotoxin B (SEB) is most often
  associated with food-borne outbreaks of GI
  disease
• Toxic shock syndrome
• Staphylococcal enterotoxins have been prepared as
  a powder for aerosol dispersal

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Staphylococcal Enterotoxin B Intoxication

• As a biologic weapon, SEB has the advantages of
  heat stability, a wide range of biologic
  activities, and high potency
• aerosol exposure to SEB, symptoms begin within 3
  to 12 hours, with sudden onset of fever,
  headache, chills, myalgias, and a nonproductive
  cough

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Staphylococcal Enterotoxin B Intoxication

• Dyspnea and retrosternal chest pain are sometimes
  evident, and a high-dose exposure can lead to
  hypotension, shock, multiorgan failure, and death
  
• Most patients will make a full recovery. Aside
  from supportive care, there is no widely
  available specific therapy for SEB toxicity

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Recognizing Terrorist Acts

• Recognition of these features is obviously more
  difficult in the setting of a covert terrorist
  attack on a civilian population than on the
  battlefield
• Early recognition is greatly enhanced by
  organized communication among point-of-contact
  health care providers, public health authorities,
  and other experts with specialized experience

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Epidemiology

• Epidemic curveIntentional attack is likely to
  differ from a curve for naturally occurring
  outbreaks
• Spikes of disease activity
• The epidemic curve pattern is particularly
  important because many biowarfare/bioterrorism
  agents will produce nonspecific symptoms that may
  be very difficult to diagnose

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Epidemiology

• Seasonal patterns
• the mosquito-borne viral encephalitides in the
  United States all tend to occur in summer or
  early fall.
• A cluster of cases during late winter might be
  suspicious
• a military attack, a prominent legal case
  decision, the anniversary of an important event
  might suggest an intentional act

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Epidemiology

• Case risk factors and zoonotic considerations(tul
  aremia in a number of urban office workers with
  no exposure to animals or animal products would
  raise suspicion)
• Geography(Ebola hemorrhagic fever, would not be
  expected to appear in patients in the United
  States )

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Conclusions

• The threat of a biologic attack against a
  civilian population is now recognized as a
  current and ongoing danger.
• economic analysis estimated an economic impact of
  26.2 billion per 100,000 persons exposed to
  anthrax in some attack scenarios
• The possibility of billions of dollars saved
  through the widespread postattack use of
  antimicrobials and vaccine

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Conclusions

• Physicians and other health care providers have
  been and will continue to be the first to
  encounter victims of a biologic weapon
• It is therefore critical that they be familiar
  with biologic warfare agents
• Further education in this area can be acquired
  through electronic media at a variety of Web
  sites and through e-mail networks

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Appendix

• The Johns Hopkins University Center for Civilian
  Biodefense Studies. www.hopkins-bioidefense.org.
  This site provides a comprehensive set of
  documents and links for useful information
  related to the commonly discussed biothreat
  agents.
• Association for Professionals in Infection
  Control and Epidemiology bioterrorism resources
  http//www.apic.org/html/resc/biomain.html.
  Provides links to useful publications and
  conferences.
• CDC bioterrorism homepage http//www.bt.cdc.gov.
  Provides a searchable database for specific
  infectious diseases, and access to MMWR
  (Morbidity and Mortality Weekly Report).
• New York City Department of Health information
  resource concerning September-October 2001
  anthrax bioterrorism http//www.ci.nyc.ny.us/html
  /doh/html/alerts/911bio.html.

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Appendix

• "Emerging Infections Network" of The Infectious
  Diseases Society of America http//www.idsociety.
  org/EIN/TOC.htm. Also bioterrorism resources for
  clinicians at the IDSA Web site. An electronic
  mail forum for dissemination of, and discussion
  about, unusual infectious disease cases and
  clusters of cases. The bioterrorism resource page
  provides links to teaching slide sets and other
  educational material.
• Medical NBC Online Information server
  http//www.nbc-med.org/others/. Extensive news
  and information for military personnel and health
  care workers regarding nuclear, biologic, and
  chemical weapons.
• ProMED http//www.promedmail.org/pls/promed/prome
  d.home or contact majordomo_at_usa.healthnet.org.
  An electronic mail news service that provides a
  fascinating glimpse of clusters and outbreaks of
  infectious diseases around the world -- followed
  in something close to "real-time." To subscribe,
  send e-mail message "subscribe promed" to the
  address above, or follow directions at the Web
  site.