Category A Agents: Biological Agents of Highest Concern

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Category A AgentsBiological Agents of Highest
Concern

• Dr. José A. Capriles Quirós, MPH, MHSA
• Professor
• Department of Health Services Administration
• UPR Graduate School of Public Health

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Learning Objectives

• Develop an awareness of the potential agents that
  might be used in a bioterrorism event
• Identify contagious agents
• Describe the types of illness caused by the
  agents
• Identify agents that might require public health
  to provide immunizations or antibiotics to
  exposed persons
• Describe how to respond if a suspicious package
  or substance is received

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WHY PUBLIC HEALTH ?

• CHEMICAL
• effects immediate and obvious
• victims localized by time and place
• overt
• illicit immediate response
• first responders are police, fire, EMS

• BIOLOGICAL
• effects delayed and not obvious
• victims dispersed in time and place
• no first responders
• unless announced, attack identified by medical
  and public health personnel

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CRITICAL BIOLOGICAL AGENTSCATEGORY A

• High priority agents that pose a threat to
  national security because they
• can be easily disseminated or transmitted
  person-to-person
• cause high mortality, with potential for major
  public health impact
• might cause panic and social disruption
• require special public health preparedness

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Biological Agents of Highest Concern Category A
Agents

• Smallpox (Variola major)
• Anthrax (Bacillus anthracis)
• Plague (Yersinia pestis)
• Tularemia (Francisella tularensis)
• Botulism (Botulinum toxin)
• Viral hemorrhagic fevers (Filoviruses
  Arenaviruses)

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CRITICAL BIOLOGICAL AGENTSCATEGORY B

• Second highest priority agents that include those
  that
• are moderately easy to disseminate
• cause moderate morbidity and low mortality
• require specific enhancements of CDCs diagnostic
  capacity and enhanced disease surveillance

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CRITICAL BIOLOGICAL AGENTSCATEGORY B

• Coxiella burnetti (Q fever)
• Brucella species (brucellosis)
• Burkholderia mallei (glanders)
• Alphaviruses
• Venezuelan encephalomyelitis
• eastern / western equine encephalomyelitis
• Ricin toxin from Ricinus communis (castor bean)
• Epsilon toxin of Clostridium perfringens
• Staphylococcus enterotoxin B

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CRITICAL BIOLOGICAL AGENTSCATEGORY B

• Subset of Category B agents that include
  pathogens that are food- or waterborne
• Salmonella species
• Shigella dysenteriae
• Escherichia coli O157H7
• Vibrio cholerae
• Cryptosporidium parvum

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CRITICAL BIOLOGICAL AGENTSCATEGORY C

• Third highest priority agents include emerging
  pathogens that could be engineered for mass
  dissemination in the future because of
• availability
• ease of production and dissemination
• potential for high morbidity and mortality and
  major health impact
• Preparedness for Category C agents requires
  ongoing research to improve detection, diagnosis,
  treatment, and prevention

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CRITICAL BIOLOGICAL AGENTSCATEGORY C

• Nipah virus
• Hantaviruses
• Tickborne hemorrhagic fever viruses
• Tickborne encephalitis viruses
• Yellow fever
• Multidrug-resistant tuberculosis

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Diseases of Bioterrorist Potential Overview
Illness and Management
CDC, AFIP
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Types of Illnesses These Agents Can Cause

• Flu-like illness (fever, sweats, nausea)
• Cough and/or pneumonia
• Skin ulcers (anthrax, tularemia, plague)
• Rashes (smallpox, ebola)
• Paralysis (botulism)
• Diarrhea vomiting (food- and water-borne
  agents)
• Headache, confusion

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Contagious Agents(Person-to-Person Transmission)

• Smallpox
• Plague pneumonia
• Some viral hemorrhagic fevers (e.g., ebola)
• Food- and water-borne agents (e.g., salmonella
  shigella)

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Agents That May Require Antibiotics or
Immunization to Prevent Disease

• Immunization
• Smallpox
• Anthrax

• Antibiotics
• Anthrax
• Plague
• Tularemia
• Q Fever
• Brucellosis

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DecontaminationCategory A Critical Agents

• Decontamination of exposed persons
• Showering or washing thoroughly with soap and
  water adequate for most bleach not necessary
• Decontamination of facilities and equipment
• May not be necessary for surfaces contaminated by
  agents with short survival time (i.e., plague,
  botulism)
• Other agents may require bleach solution,
  sporicidal chemicals, incineration, and/or
  autoclaving

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Infection Control Category A Critical Agents

• Infection control
• Standard precautions all cases
• Airborne contact precautions smallpox and
  viral hemorrhagic fevers
• Droplet precautions pneumonic plague

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Infection ControlStandard Precautions

• Standard Precautions all cases
• Disposable, non-sterile gloves
• Hand washing after glove removal
• Disposable gown or apron, faceshield if splashing
  anticipated
• Change protective gear between cases

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Infection Control Contact Precautions

• Standard precautions plus
• Wear gloves and gown, change after contact with
  infectious material
• Dedicate non-critical patient care items (e.g.,
  stethoscope) to a single patient or disinfect
  between patients

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Infection Control Droplet and Airborne
Precautions

• Airborne Precautions
• Standard Precautions plus
• Patient in negative air pressure room
• Wear respiratory protection (such as a HEPA
  filter mask)

• Droplet Precautions
• Standard Precautions plus
• Wear mask when w/in 6 ft of patient

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Summary of Key Points

• Most of the biological agents of concern produce
  an initial non-specific or flu-like illness.
• Standard precautions should be used with all
  patients following a bioterrorism incident.
• Additional precautions are required with a few
  biological agents, where person-to-person
  transmission is possible.

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BIOTERRORISM AND THE PUBLIC HEALTH SECTOR

• CONCLUSIONS
• Preparation for a biological mass disaster
  requires coordination of diverse groups of
  medical and non-medical personnel
• Preparation can not occur without support and
  participation by all levels of government
• Preparation must be a sustained and evolutionary
  process

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Clinical ManifestationsCategory A Agents
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Anthrax as a BW Agent

• Disease of herbivores
• Gram positive bacillus
• Hardy spores
• Easy to grow
• Easily aerosolised
• 1-5 ? particles
• Mortality 65-85 overall
• No person-to-person spread
• Humans and animals
• Environmental persistence

(CDC Public Health Image Library)
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Inhalational AnthraxKey Features (1)

• ID50 10,000 spores
• Incubation usually 1-6d (but may be as long as
  60d)
• 2 stage illness
• Flu-like prodrome (2-5 d)
• Abrupt onset respiratory failure (1-2 d later)
• CXR lobulated mediastinal widening, may have
  infiltrates

(Dept. Radiologic Pathology, AFIP
http//anthrax.radpath.org)
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Cutaneous Anthrax

• 95 of naturally occurring cases
• Subcutaneous inoculation of spores
• Hands, forearm, head
• Incubation lt1 to 7 days
• Small painless papule ? ulcer with marginal
  vesicles (24-48h)
• Painless oedema surrounds lesion
• Develops into eschar (2-6 d)
• Untreated mortality 20(treated v. rare)

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Intestinal Anthrax

• Ingestion of contaminated meat
• Incubation lt1 - 7 days
• Fever, acute abdomen, vomiting, bloody
  diarrhoea
• Intestinal eschar (similar to cutaneous lesion)
• Progression to sepsis syndrome
• Mortality 50 - 100 despite treatment

(Armed Forces Institute of Pathology, USA)
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Anthrax Treatment

• Only early treatment improves prognosis if
  inhalation anthrax
• Ciprofloxacin or doxycycline plus one (or two)
  other antibiotics, initially IV
• ( rifampicin, vancomycin, chloramphenicol,
  penicillin, amoxycillin, imipenem, clindamycin,
  clarithromycin,)
• Prolonged treatment - antibiotics for 60 days
• Resistant to cephalosporins

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Botulism Categories

• Foodborne botulism
• caused by eating foods that contain botulism
  toxin
• Intestinal botulism (infant and child/adult)
• caused by ingesting spores of the bacteria which
  germinate and produce toxin in the intestines
• Wound botulism
• C. botulinum spores germinate in the wound
• Inhalation botulism
• Aerosolized toxin is inhaled
• does not occur naturally and may be indicative of
  bioterrorism

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Botulism Pathogenesis

• Incubation period
• ingestion unknown
• foodborne 6 hours-8 days
• wound 4-14 days
• inhalation (estimated) 24-36 hours
• Toxin enters bloodstream from mucosal surface or
  wound
• Binds to peripheral cholinergic nerve endings
• Inhibits release of acetylcholine, preventing
  muscles from contracting
• Symmetrical, descending paralysis occurs
  beginning with cranial nerves and progressing
  downward

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Botulism Clinical Presentation

• Classic symptoms of botulism poisoning include
• blurred/double vision
• muscle weakness
• drooping eyelids
• slurred speech
• difficulty swallowing
• patient is afebrile and alert
• Infants with botulism will present with
• weak cry
• poor feeding
• constipation
• poor muscle tone, floppy baby syndrome

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Botulism Clinical Treatment

• Antitoxin administration
• Supportive Care
• mechanical ventilation
• body positioning
• parenteral nutrition
• Elimination
• Induced vomiting
• High enemas

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Botulism Transmission

• Home-canned goods (foodborne)
• particularly low-acid foods such as asparagus,
  beets, and corn
• Honey (ingestion)
• can contain C. botulinum spores
• not recommended for infants lt12 months old
• Crush injuries, injection drug use (wound)

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Plague Epidemiology

• Caused by Yersinia pestis
• About 10-15 cases/year U.S.
• Mainly SW states
• Human plague occurs from bite of an infected flea
  (bubonic)
• Only pneumonic form of plague is spread
  person-to-person

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Plague Clinical Forms

• Bubonic plague
• Most common naturally-occurring form
• gt80 bacteremic 25 clinically septic
• Mortality 60 untreated, lt5 treated
• Primary or secondary septicemic plague
• Pneumonic plague
• Most likely BT presentation
• From aerosol or septicemic spread to lungs
• Survival unlikely if treatment not initiated
  within 24 hours of the onset of symptoms

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Pneumonic PlagueClinical Presentation

• Incubation 1-6 days (usually 2-4 days)
• Acute onset of fever with cough and dyspnea,
  chest pain
• Hemoptysis characteristic watery or purulent
  sputum also possible
• Prominent GI symptoms may be present, including
  nausea, vomiting, diarrhea, and abdominal pain

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Pneumonic Plague Radiological Lab Findings

• CXR variable, but frequently bilateral
  infiltrates, patchy or consolidated
• Leukocytosis w/bandemia (PMNs)
• Often fibrin split products liver enzymes may be

Source Centers for Disease Control and
Prevention, Division of Vector-Borne Infectious
Diseases, Fort Collins, CO
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When to Think (BT) Plague?

• Other recent cases of plague
• Claims by a terrorist or aggressor of a release
  of plague
• Illness in persons with common ventilation system
  or other exposure
• Cluster of similar or unusual syndrome compatible
  with plague
• More severe disease than is usually expected or
  failure to respond to standard therapy
• Unusual season for pneumonia in presenting age
  group

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Plague Infection Control

• Person-to-person transmission via respiratory
  droplets
• Standard respiratory droplet precautions include
  disposable surgical masks, gown, gloves and eye
  protection
• Case isolation for at least the first 48 hrs of
  antimicrobial therapy
• Bubonic plague standard precautions
• Strict precautions when handling bodies of plague
  victims
• Use HEPA respirators and negative pressure rooms,
  if available

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Tularemia - Overview

• Bacterial zoonosis caused by Francisella
  tularensis
• First identified in 1911 as plague-like illness
  of ground squirrels in Tulare County, CA
• Multiple routes of human infection
• Clinical signs and severity of illness depend on
  route of transmission and strain

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Clinical Syndromes of Tularemia
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Clinical Syndromes of Tularemia
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Treatment

• Aminoglycosides are bactericidal
• Streptomycin 7.5-15 mg/kg IM q12 hrs for 7 to 14
  days
• Gentamicin 3-5mg/kg/day IV for 7-14 days with
  peak levels of at least 5.0 ?g/ml
• Doxycycline and ciprofloxacin also effective
• Tetracycline and chloramphenicol are
  bacteriostatic

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Prophylaxis

• A live attenuated vaccine is available as an
  investigational agent
• Antibiotic prophylaxis following exposure is not
  generally recommended
• Exposed persons should be watched for fever
  (gt37C). Antibiotic therapy should be initiated
  promptly if fever develops

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Infection Control for Patients

• No human-to-human transmission of tularemia
• Standard precautions are appropriate
• Isolation of patients is not recommended
• Bodies of patients should be handled using
  standard precautions
• Autopsy procedures likely to produce aerosols
  should be avoided
• Clothing and linens contaminated with body fluids
  should be disinfected per standard hospital
  protocols

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Prevention

• Avoid tick- infested areas
• Protective clothing, repellents, tick checks
• Use gloves, masks, protective eye-cover when
  handling wild animals
• Cook wild game thoroughly
• Standard precautions for handling drainage from a
  wound or the eyes in patients with tularemia

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SMALLPOX -Why is it a threat?

• Potential clandestine stockpiles
• Satisfy most criteria of a good BW
• Aerosol infectivity highly infectious
• Communicability
• Long incubation period
• Potential for large scale production
• Highly pathogenic high mortality
• Lack of population immunity
• Limited vaccine no treatment
• Very limited diagnostic capability

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SMALLPOX Clinical Presentation (I)

• Most (all?) primary infections clinically
  apparent
• Variola in partially immune ? milder illness,
  scant atypical or
• no rash
• Clinical presentation
• Severe prodrome 2-5 days high fever, malaise,
  prostration, headache, backache cough uncommon
• Patient very toxic usually confined to bed
• Characteristic rash
• Begin 2-5 days post-onset of fever evolution
  over 10-14 day period
• 5 Stages

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Smallpox Lesion Development and Fever Progression
Source WHO
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Smallpox vs. Chickenpox

• The particular points that help to differentiate
  smallpox from chickenpox the fever precedes
  the rash by 2 to 4 days, the pocks on any part
  of the body are at the same stage of
  development, and they develop slowly, the pocks
  are more numerous on the arms and legs than on
  the body, the pocks are usually present on the
  palms and soles, death following smallpox is
  not uncommon, while in chickenpox death is very
  rare.

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