1. “Preparing Our Communities”
Welcome!
-Introduction of instructor
-Can everyone hear me? (adjust microphone/close doors)
-Can everyone see the screen? (adjust focus/lighting)
-Announcement of first lecture topic
-students may follow along in their textbooks....Chapter 1

2. Faculty Disclosure
For Continuing Medical Education (CME) purposes as required by the American Medical Association (AMA) and other continuing education credit authorizing organizations:
In order to assure the highest quality of CME programming, the AMA requires that faculty disclose any information relating to a conflict of interest or potential conflict of interest prior to the start of an educational activity.
The teaching faculty for the BDLS course offered today have no relationships / affiliations relating to a possible conflict of interest to disclose. Nor will there be any discussion of off label usage during this course.

3. Biological Events
Chapter 5 3 3

4. Objectives
Describe the difference between biological events and bioterrorism (BT)
Discuss public health BT surveillance
Identify the CDC BT Category A agents
Identify emerging infectious diseases
Compare and contrast BT and other CBRNE WMD utilizing the DISASTER paradigm 4 4

5. Biological Events Intentional Natural
Biological events: Natural vs. Intentional
Release of anthrax in mail
Salmonella sprayed on food bar
Smallpox infection
Aerosolized botulinum toxin
Intentional
Natural
Outbreak of monkey pox in pet prairie dogs
Avian Flu pandemic
Natural occurrence of anthrax
Bubonic plague outbreak
This slide presents two cases, lecturer should read the cases and discuss which scenario seems to be a natural biological event and which seems to be intentional. The slides will indicate the right answer. This allows for lead into a discussion of what Bioterrorism is. 5 5

6. Bioterrorism Release Types: Overt or Covert
Covert or Overt ?
Covert or Overt ?
Notice of release provided
May contain a threat
Designed to create panic or fear
May be hoax (white powder) or credible threat
Overt
Covert Release
No notice or threat
Difficult to detect
Persons seek care at usual medical care facilities
Early symptoms non-specific
so detection may be delayed
Focus: Astute clinician make diagnosis and notify health department (Detection)
(1763)Captain Simeon Ecuyer had sent smallpox-infected blankets and handkerchiefs to the Indians surrounding the fort (as a supposed peace offering)-- but actually an early example of biological warfare -- which started an epidemic among the Indians.
The biological event may result from a covert release of a pathogen into the environment, or it may be heralded by the receipt of an object, such as a package or piece of mail, accompanied by a warning or threat, or initiated as a witnessed or announced release of the pathogen into the environment, thereby exposing those persons who are present. Two quick cases presented one using overt and one using covert. Lecturer needs to explain the word covert and overt. Overt is openly done, attracting attention to the task. Covert is in a hidden means so people don’t know it is happeneing until too late.
Letter sent to the New York Post and NBC News:
Containing “white powder” 6 6

7. Potential Methods of Detection
Public Health Surveillance
Increased number of patients
Increased unexplained deaths
Unusual patient age distribution
Unusual seasonality
Unusual manifestation of disease
Animal die-off
Notifiable disease reporting by physicians & other providers
Automated reporting of laboratory results
Number and type of 911 calls
Number and type of EMS runs
Syndromic surveillance
In addition to an increased number of patients, other clues that may signal a covert bioterrorism attack include an increase in unexplained deaths, unusual age distribution of the patients (eg, severe illness among persons 20 to 50 years old), unusual seasonality (eg, severe widespread respiratory illness during the summer months), an unusual manifestation of disease (eg, inhalational anthrax), or the occurrence of an animal die-off (eg, the death of crows heralding the arrival of West Nile virus in New York City in 1999). 7 7

8. CDC Categories BT Agents
Divided into Categories A, B,C based on:
Quantity of agent available
Ability to disseminate the agent
Person-to-person transmission
Severity of disease
Public response, panic, etc..
Overall risk to national security 8 8

9. Category A Agents Anthrax Smallpox Plague Botulinum toxin Tularemia
Viral hemorrhagic fevers
The US public health system and primary health care providers must be prepared to address various biological agents, including pathogens that are rarely seen in the United States. High-priority agents include organisms that pose a risk to national security because they:
can be easily disseminated or transmitted from person-to-person;
result in high mortality rates and have the potential for major impact on public health;
might cause public panic and social disruption; and
require special action for public health preparedness. 9 9

10. Category B Agents (examples)
Infectious Agents
Brucellosis
Glanders
Why are these Category B Agents
Less quantity available than Category A
Harder to disseminate
Less person to person transmission- if any
Slightly less severity of disease
Less known to public - therefore less likely to cause panic
Slightly less risk to National Security
Bio-toxins
Ricin toxin from Ricinus communis (castor beans)
Staphylococcal enterotoxin B
Water safety threats
Vibrio cholerae
Food safety threats
Salmonella species
Escherichia coli O157:H7
Shigella
The second highest priority agents include those that:
are moderately easy to disseminate;
result in moderate morbidity rates and low mortality rates; and
require specific enhancement of CDC's diagnostic capacity and disease surveillance.
Viral encephalitis
Venezuelan Equine Encephalitis 10 10

11. Category C Emerging infectious diseases as bioterrorism agents
Nipah virus
Hantavirus
Emerging infectious disease that posses a significant public health threat
Avian Flu
SARS
The third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future due to:
availability;
ease of production and dissemination; and
potential for high morbidity and mortality rates and major health impact.
Although not yet classified as a potential agent of BT, SARS demonstrated the potential threat from an emerging pathogen during the outbreak in spring of 2003 11 11

12. Category A: Anthrax
Endemic in animals worldwide with occasional human cases
Handling infected animal products (especially cattle, sheep, horses, mules and goats)
Spores used for bioattack
Aerosolized directly or sent in mail/packages
Three forms
Cutaneous, Inhalation, GI
Anthrax in CSF—US index case 12 12

13. Anthrax – Clinical Features
Inhalation
Incubation: 2-43 days (may be longer)
Prodrome
Fevers, malaise, dry cough, chest pain, dyspnea, myalgia
Abrupt onset of fulminant illness
Sudden high fever, respiratory distress, shock
Meningitis in ~50%
Actual pneumonia uncommon
Incubation Period: 2 to 43 days (May be longer)
Presentation:
Patients present initially with a “flu like “illness, consisting of fever, not feeling well, fatigue, cough, shortness of breath, headache, anorexia, and chest pain. Upper respiratory symptoms, such as a runny nose or sore throat, can occur but are not typical (10-20% of patients). This phase lasts from hours to a few days. If left untreated, the patients develop a sudden increase in fever, severe respiratory distress, diaphoresis and shock.
The chest x-rays are abnormal, with mediastinal widening (70%), infiltrates (70%), and pleural effusions (80%). 13 13

14. Widened mediastinum & pleural effusions
Normal Chest X-Ray
Widened mediastinum & pleural effusions
Inhalational anthrax US index case 14 14

15. Anthrax – Clinical Features
Cutaneous
Incubation: 1 to 7days (up to 12 days)
Erythematous “itchy” papule  ulcer  characteristic black eschar with surrounding erythema and edema
Regional adenopathy and systemic symptoms (e.g., fever, malaise)
Most lesions completely resolve
Incubation Period: 1 to 7days (May be as long as 12 days)
Presentation:
The sore is initially a small itchy papule or vesicle, but by the second day it becomes an ulcer. The sore usually is on an exposed area of the body. Non-tender swelling surrounds the ulcer. Other small vesicles may surround the ulcer. Over the next 1 to 2 days a black scab forms, which falls off after about 2 weeks. In about % of patients the lesion completely resolves. Extensive swelling (edema) and tender lymph nodes may occur. Patients will likely have fever. 15 15

16. Anthrax – Clinical Features
Gastrointestinal
Incubation period 1-7 days
Not likely after a bioattack
Presents as febrile illness with bloody diarrhea
Eating undercooked infected meat
Incubation Period: 1-7 days
Presentation:
This form of anthrax occurs following the eating of undercooked infected meat. It is much less likely than the other forms to occur following a biological attack. GI Anthrax presents as febrile illness with nausea, vomiting and subsequently bloody diarrhea. 16 16

17. Anthrax Diagnosis Blood cultures Usually positive in < 24h
Gram stain pleural fluid or CSF
Sputum gram stain/culture is usually NOT positive
Inhalational disease
Very suggestive if fever and widened mediastinum
Cutaneous disease
Culture fluid from under eschar
Nasal swabs are a poor test
The first clue may be several patients presenting with a severe pulmonary illness as described above.
Blood cultures should be done prior to administration of antibiotics, and are usually positive in less than 24 hours (h). Gram positive bacilli with a preliminary identification as a Bacillus species in the setting of meningitis, pneumonia or sepsis should be evaluated for anthrax and sent to a public health laboratory that is a part of the Laboratory Response Network (LRN).
Gram stain of pleural fluid or cerebrospinal fluid (CSF) may also be helpful
Sputum is usually NOT positive by stain or culture
Fever and widened mediastinum on chest radiograph (CXR) or computed tomography (CT) is very suggestive
For cutaneous disease, culture fluid from under eschar
Nasal swabs are a poor test to rule out anthrax and should NOT be used as a clinical test. They cannot rule out infection. One patients with a negative swab died from anthrax during the fall of 2001. 17 17

18. Anthrax –Treatment Ciprofloxacin 400 mg IV q12h
10-15 mg/kg for children
Other fluoroquinolones probably also effective OR
Doxycycline 100 mg IV q12h
2.2 mg/kg for children
PLUS
1 or 2 additional antibiotics
Clindamycin, rifampin, vancomycin, penicillin, chloramphenicol, imipenem, or clarithromycin
Early antibiotic treatment is essential for survival. A high-risk individual who is symptomatic needs to be started on appropriate antimicrobial therapy immediately without waiting for confirmatory laboratory tests. 18 18

19. Prophylaxis and Infection Control
Ciprofloxacin 500 mg PO BID(Peds:10-15 mg/kg) or
Doxycycline 100 mg PO BID (Peds:2.2 mg/kg)
Continue for 60 days (? 100 days)
Vaccine available for DOD forces
Infection Control
Standard barrier precautions are needed
Not transmitted person-to-person
Only immunize / prophylaxis exposed at BT attack
Prophylaxis (also for cutaneous disease and for inhalational disease in mass casualty setting where IV administration is not feasible)
Ciprofloxacin 500 mg PO BID (10 to 15 mg/kg/dose for children) or
doxycycline 100 mg PO BID (2.2 mg/kg/dose for children)
Continue for 60 days or until the third dose of vaccine given if available
Infection control
Standard barrier precautions are needed
Anthrax is not transmitted by person to person contact. Patients do not need to be in Airborne isolation
No need to immunize or provide prophylaxis to contacts unless they were exposed at time of the BT attack
Need to contact hospital epidemiologist, microbiology laboratory and state health department immediately 19 19

20. Anthrax Vaccination Schedule1 2 3 4 5 6
4 weeks
2 weeks
6 months
12 months
18 months
6 shots over 18 months, then annual booster
Dosing schedule is 0.5 mL subcutaneously at each visit
Then yearly boosters
Anthrax Vaccination Schedule. The recommended schedule for vaccination is 6 subcutaneous 0.5 mL doses given at day 0 (D-0), 2 weeks (D+14D), 4 weeks (D+28D), 6 months (D+6M), 12 months (D+12M), and 18 months (D+18M). Annual booster doses of 0.5mL are required to maintain immunity (note 14). 20 20 19

21. Clostridium botulinum
Botulism
Clostridium botulinum
A Toxin Producing Obligate, Anaerobic, Spore Forming,
Gram Pos. Bacillus 21 21

22. Botulism - General Caused by a toxin produced by Clostridium botulinum
Sporadic cases and outbreaks caused by tainted foods
For bioattack toxin could be delivered as an aerosol or used to contaminate food / water
Botulism is caused by a toxin produced from the bacteria Clostridium botulinum. This toxin is the most poisonous substance known, producing paralysis in its victims. Sporadic cases and outbreaks do naturally occur due to tainted foods. In a biological attack toxin could be delivered as an aerosol or used to contaminate food and water supplies. 22 22

23. Botulism - Clinical Features
12 to 36 hour “incubation”
Range 2 h to 8 days
Clinical recognition is key to diagnosis
Bulbar palsies: Must be present!
Ptosis, blurred vision, dry mouth, dysarthria, trouble swallowing
Afebrile,“AAO x 3”, difficulty speaking
Descending skeletal muscle paralysis
Death: Respiratory muscle paralysis
Incubation Period: 12 to 36 hour (range 2 h to 8 days)
Presentation:
Patients present with bulbar palsies. Specifically they have ptosis (drooping of the upper eyelid), blurred vision, dry mouth, difficulty speaking, and trouble swallowing. It is not possible to have botulism without the multiple cranial nerve palsies. This fact is helpful in distinguishing botulism from other diseases such as Guillain-Barré, Miller-Fisher syndrome, myasthenia gravis, or a disease of the central nervous system.
Patients are not febrile.
Patients are not confused or obtunded, but may have difficulty speaking.
Rapidity of onset and severity are dependent on the amount of toxin absorbed.
Subsequently patients develop descending symmetrical skeletal muscle paralysis.
Death results from respiratory muscle paralysis. 23 23

24. 17 Year-Old with Mild Botulism
A, Patient at rest. Note bilateral mild ptosis, dilated pupils, disconjugate gaze, and symmetric facial muscles. B, Patient was requested to perform his maximum smile. Note absent periorbital smile creases, ptosis, disconjugate gaze, dilated pupils, and minimally asymmetric smile. As an indication of the extreme potency of botulinum toxin, the patient had 40 x 10-12g/mL of type A botulinum toxin in his serum (ie, 1.25 mouse units/mL) when these photographs were taken. 24 24

25. Botulism - Treatment Supportive care Respiratory failure Antitoxin
Prolonged Ventilator support
Antitoxin
State health department obtained
Prevents further damage
Does not alter current damage
Treatment
Supportive care including intensive care with close monitoring of respiratory function, ventilator support for respiratory failure, enteral feeding tubes, and treatment of secondary infections
Antitoxin is available through state health departments. As the dose and safety precautions for the antitoxin have changed over time, clinicians should review instructions with a public health authority prior to its use.
Recovery takes weeks to months. 25 25

26. Botulism – Infection Control
Prophylaxis
No proven prophylaxis at this time
Investigational Vaccine
Isolation
Standard precautions (not P-to-P)
Need to contact public health authority immediately: Others may be exposed to contaminated food source or agent
There is no proven prophylaxis at this time
Infection Control
Standard precautions
Need to contact hospital epidemiologist and public health authority immediately, as this is a public health emergency. Other individuals could be exposed to the contaminated food source if they are not notified. 26 26

27. Plague Yersinia pestis Yersinia pestis
Note characteristic “safety pin appearance” of Yersinia pestis, the causitive agent of the plague as seen on this Wayson stain of blood
Yersinia pestis
Source:
Gram Neg., Anaerobic, Rod Shaped Bac.
“Safety Pin” Bipolar on Wright Staining 27 27

28. Plague - General Buboes Endemic in animals throughout the world
Prairie dogs in the Southwestern US
High potential as a BT agent
Endemic form
Spread to humans via a flea vector
Results in bubonic form of the disease
Bioattack
Most likely aerosolized
Results in pneumonic plague
Release of infected fleas
Buboes
Source:
Plague is caused by the bacteria Yersinia pestis. This organism has a high potential to be used as a BT weapon, as it is endemic in many animals (including prairie dogs in the southwestern United States) throughout the world, is easy to grow and disseminate, has a high fatality rate, and can be spread from person to person. The endemic form is spread to humans via a flea vector leading to the bubonic form of the disease. For a biological attack the bacteria would most likely be aerosolized, leading to pneumonic plague.
Photo: prairie dog 28 28

29. Plague – Clinical Features
Following Aerosolized Bioattack
1- 6 day incubation
Abrupt onset
High fever, chills, and malaise
Cough with bloody sputum
Sepsis
Severe rapidly progressive pneumonia
Untreated 100% mortality
Plague following a BT attack would present differently than natural occurring plague. BT plague would present as follows:
Incubation Period: 1 to 6 day incubation
Presentation: Abrupt onset of high fever, chills, malaise, shortness of breath, cough with bloody sputum, sepsis. Patients may also have nausea, vomiting and diarrhea
Patients subsequently develop a severe rapidly progressive pneumonia 29 29

30. Plague - Diagnosis CXR with patchy infiltrates
Culture of blood and sputum
Need to inform the laboratory if you suspect plague … special techniques
May show characteristic “safety-pin” bipolar staining
Sudden # Gm(neg) pneumonia
CXR has patchy infiltrates
Culture of blood and sputum. The laboratory needs to be notified of the suspicion of plague, as special culturing techniques may be needed.
Gram stain may show characteristic “safety-pin” bipolar staining 30 30

31. Normal Chest X-Ray
Plague pneumonia 31 31

32. Plague - Treatment Streptomycin 1 g IM q12h
Preferred: Start within first 24 hours for 10 days
Streptomycin 1 g IM q12h
15 mg/kg/dose for children
Avoid in pregnant women
Gentamicin 5 mg /kg IM or IV qd
Or 2 mg/kg load the 1.7 mg/kg q8h
For children use 2.5 mg/kg q8h
Alternative
Doxycycline 100 mg IV q12h
2.2 mg/kg/dose q12h for children
Ciprofloxacin 400 mg IV q12h
Other fluoroquinolones probably effective
For children 15 mg/kg/dose q12h
Treatment
Preferred choices
Streptomycin 1 g intramuscularly (IM) q 12h (15 mg/kg/ dose up to 1 gm maximum dose q12 h for children)
Gentamicin 5 mg/ kg IM or IV q day (or 2 mg/kg load then 1.7 mg/kg q 8h; for children 2.5 mg/kg q 8h)
Alternate choices
Doxycycline 100 mg IV q 12h (2.2 mg/kg/ dose q 12 h up to maximum dose of 200 mg/d for children)
Ciprofloxacin 400 mg IV q 12h (children 15 mg/kg/dose every 12 h; other fluoroquinolones probably effective)
Choloramphenicol 25 mg/kg IV q 6h for adults and children
Pregnant women: Gentamicin is the preferred choice, followed by doxycycline and ciprofloxacin at the above doses. Avoid streptomycin 32 32

33. Plague - Infection Control
Prophylaxis: Treat for 7 days
Doxycycline 100 mg PO bid
2.2 mg/kg for children
Ciprofloxacin 500 mg PO bid
20 mg/kg for children
other fluoroquinolones probably effective
Isolation
Droplet precautions (Yes, P-to-P)
Prophylaxis
Preferred choices:
Doxycycline 100 mg PO BID (2.2 mg/kg/ dose up to 100 mg maximum twice a day for children)
Ciprofloxacin 500 mg PO BID (20 mg/kg/dose up to 500 mg maximum twice a day for children; other fluoroquinolones probably effective)
Alternative choice
Chloramphenicol 25 mg/kg orally 4 times a day (Not to be used in children under the age of 2 yrs)
Pregnant women: treat as above
Treat for 7 days
Infection Control
Patients with pulmonary plague are can be contagious.
Use droplet precautions for first 48 h and clinically better
The microbiology laboratory needs to be promptly notified for their protection
The hospital epidemiologist and public health authorities need to be immediately 33 33

34. Smallpox
Source: 34 34

35. Smallpox - General One of the deadliest disease
Mortality rate of 30%
US stopped vaccinating in 1972
Declared eradicated by WHO
In 1980, however...
Bioattack
Aerosolized virus or by exposure to purposefully infected terrorists
General
Smallpox, once one of the deadliest diseases known to mankind with a mortality rate of 30%, fell victim during the 1960s and 70s to an aggressive and successful multinational vaccination program, enabling the World Health Organization to declare the disease eradicated in With routine vaccination against smallpox ceasing in 1972 in the United States (over 30 years ago) we now have a large population that would be very susceptible to this disease. Following a BT attack utilizing this agent, smallpox would be expected to spread rapidly and widely throughout the world. A biological attack could be via aerosolized virus or by exposure to purposefully infected terrorists. 35 35

36. Smallpox - Clinical Features
Incubation period
7-17 day (average 12d), Weaponized 3-5 d
Severe prodrome Key difference!
2-3 day of fever, severe myalgias, prostration, occ. n/v, delerium
10% with light facial erythematous rash
Distinctive rash
Initially on face and extremities
Including palms and soles
Spreads to trunk
Clinical features
Incubation Period: 7 to 17 day incubation (average 12 days)
Presentation:
Prodrome: Smallpox patients have a severe prodrome lasting 2 to 3 day prior to the development of the rash. This prodrome consists of fever, severe myalgia, prostration, occasionally nausea and vomiting, and delirium. This prodrome is one of the key distinguishing features between smallpox and chickenpox. 10% of patients will have a light facial erythematous rash. 36 36

37. Small Pox - Clinical Features
Rash
Macules  papules  vesicles  pustules
Unlike chicken pox, lesions don’t appear in “crops”
All lesions in an area are in the same stage of development
Lesions are firm, deep, frequently umbilicated
Rash scabs over in 1-2 weeks
Rash: The smallpox rash is distinctive (seen in next slide). It develops initially on face and extremities (including palms and soles), and then spreads to trunk. The rash starts as macules, and then evolves into papules, vesicles, and finally pustules. All lesions are in the same stage of development.
These lesions are firm, deep, and frequently umbilicated. The rash scabs over in 1 to 2 weeks, resulting in scars.
Chickenpox
Smallpox
Source: 37 37

38. The main diagnostic tool for smallpox is the history and physical!
Source: 38 38

39. Smallpox - Treatment Vaccination Supportive care
In the early stages of disease
Supportive care
Penicillinase-resistant antibiotics (for secondary infection)
Daily eye rinsing
Adequate hydration and nutrition
FDA has not approved specific therapy
Topical idoxuridine for corneal lesions (Dendrid)
Cidofovir ?
Treatment
Patients should be treated in a negative pressure room
Patient should be vaccinated against smallpox, especially if in the early stages of disease
Supportive care;
Penicillinase-resistant antibiotics if:
smallpox lesions are secondarily infected
bacterial infection endangers the eyes,
the eruption is very dense and widespread.
Daily eye rinsing
Adequate hydration and nutrition
Specific Therapy
No specific therapy has been FDA approved.
Topical idoxuridine (Dendrid, Herplex, or Stoxil) may be useful for the treatment of corneal lesions (efficacy is unproved)
Cidofovir :
This antiviral medicine is licensed for the treatment of cytomegalovirus.
Animals suggest that cidofovir it be usefull in the treatment of smallpox.
Could be made available under an investigational-new-drug protocol for smallpox or adverse effects 39 39

40. Smallpox - Infection Control
Prophylaxis
Vaccine is effective if given within 3 days of exposure
Isolation
Airborne and contact precautions
Febrile illness after potential exposure should prompt isolation before rash starts
Immediate contact your hospital epidemiologist and the public health authorities 40 40

41. Francisella tularensis
Tularemia
Source:
Gram Neg. Coccobacillus 41 41

42. Tularemia - General Endemic in North America and Eurasia
Sporadic human cases spread by ticks or biting flies
Occasionally from direct contact with infected animals (ulceroglandular)
Bioattack
Aerosolized bacteria
Typhoidal tularemia & (+ / - ) pneumonia
Tuleremia is a bacterial infection that is endemic in North America and Eurasia. Sporadic human cases occur following spread by ticks or biting flies, and occasionally from direct contact with infected animals. Tuleremia has previous been developed as a biological weapon by several countries in the past. Biological attack with this agent would most likely occur via aerosolized the bacteria, resulting in typhoidal tularemia with or without pneumonia. 42 42

43. Tularemia - Clinical Features
Bioattack
3-5 day incubation (range 1-14 days)
Acute febrile illness with prostration
~80% will have radiographic evidence of pneumonia
May have associated conjunctivitis or skin ulcer & regional adenopathy
Clinical features
Incubation period: 3 to 5 day (range 1 to 14 days)
Presentation following a BT event:
Acute febrile illness with prostration
Approximately 80% of cases will have radiographic evidence of pneumonia in 1 or more lobes
May have associated conjunctivitis or skin ulcer with regional adenopathy 43 43

44. Tularemia - Diagnosis Culture of blood and sputum
May take weeks to isolate and ID
Gram negative coccobacillus
Confirmation may require reference laboratory
Potential hazard to laboratory personnel
Laboratory must be notified if tularemia is suspected
Diagnosis
Culture of blood and sputum (Note: Isolation and identification of this organism can take several weeks)
Gram negative coccobacillus—confirmation may require reference laboratory
Promptly notify laboratory personnel whenever tularemia is suspected, as special safety precautions and diagnostic procedures are required.
Public Health Laboratories that are part of the LRN have other diagnostic tools such as the polymerase chain reaction (PCR) and antibody tests to help identify this pathogen. 44 44

45. Tularemia - Treatment Preferred Treatment time varies with Abx
Streptomycin 1 g IM q12h
15 mg/kg for children
Gentamicin 5 mg / kg IM or IB q day
for children use 2.5 mg/kg q8h
Alternative
Doxycycline 100 mg IV q12h
2.2 mg/kg for children
Ciprofloxacin 400 mg IV q12h
Children 15 mg/kg
Other fluoroquinolones probably effective
Treatment
Preferred choices
Streptomycin 1 g IM q 12h (15 mg/kg/dose up to 1 g maximum q 12 h for children)
Gentamicin 5 mg/kg IM or IV q day (for children use 2.5 mg/kg q 8h)
Alternative choices
Doxycycline 100 mg IV q12 h (2.2 mg/kg/ dose up to 100 mg BID maximum for children)
Ciprofloxacin 400 mg IV q12 h (for children 15 mg/kg/ dose up to 400 mg q 12 h maximum; other fluoroquinolones probably effective)
Choloramphenicol 15 mg/kg q 6h (Not for children under age 2 yrs)
Pregnant Women: Gentamicin is be preferred over streptomycin 45 45

46. Tularemia - Infection Control
Prophylaxis: Treat for 14 days
Doxycycline 100 mg PO bid
2.2 mg/kg for children
Ciprofloxacin 500 mg PO bid
15-20 mg/kg for children
Tetracycline
Isolation:
Standard precautions (Not P-to-P)
Prophylaxis
Doxycycline 100 mg PO BID (2.2 mg/kg/dose up to 100 mg BID for children)
Ciprofloxacin 500 mg PO BID (15 mg/kg/dose for children; other fluoroquinolones probably effective)
Treat for 14 days
Infection Control
Tularemia is not spread person to person.
Standard precautions should be utilized
Patients do not need to be in airborne, droplet or contact isolation
Microbiology personnel, the hospital epidemiologist, and public health authorities must be immediately notified on suspicion of tularemia 46 46

47. Viral Hemorrhagic Fevers
Source:
Ebola virus 47 47

48. VHF - General Naturally occurring disease
Transmitted to humans by contact with infected animals or arthropod vectors.
Sporadic outbreaks in Africa, parts of Asia and Europe (Outside of Africa, likely BT event)
VHF viruses as bioterrorism agents
Weaponized by several countries
Aerosolization
Case fatality rates
Omsk hemorrhagic fever 0.5%
Ebola 90%
VHF viruses are transmitted to humans by contact with infected animals or arthropod vectors. In some cases, the arthropod vector has not yet been determined. These viruses have been weaponized by several counties in the past. Sporadic outbreaks of these infections occur in Africa, and rarely in parts of Asia and Europe. A BT attack most likely would occur from aerosolized virus. Case fatality rates range from 0.5% for Omsk hemorrhagic fever to 90% for Ebola. 48 48

49. VHF - Clinical Features
Incubation days
Depends on virus
Initial presentation
Nonspecific prodrome (fever, myalgias, headache, abdominal pain, prostration)
Exam may show only flushing of face and chest, conjunctival injection, and petechiae
Disease progresses to generalized mucous membrane hemorrhage and shock occurs
Clinical features
·           Incubation Period: 2 to 21 days, depending on the virus.
·           Presentation:
Depending on the virus, a variety of clinical manifestations could occur following a BT attack with one of the VHF viruses. Initial differentiation between these viruses following an attack would not likely be possible on clinical grounds alone.
Early in the course of the disease patients develop a nonspecific prodrome with fever, headache, arthralgias, myalgia, abdominal pain, and diarrhea. Initial exam may show only flushing of face and chest, conjunctival injection , a rash and petechiae .
Patients subsequently develop hypotension, relative bradycardia, rapid breathing, conjunctivitis, and pharyngitis. They develop progressive generalized bleeding problems mucous membrane hemorrhage, and shock. Bleeding problems include a hemorrhagic or purple rash, nose bleeds, vomiting blood, coughing up blood, and blood in stools.
If 2 of the above hemorrhagic symptoms occurs in a severely ill febrile patient (temperature greater than 101˚ F), who has been ill less than 3 weeks and has no other obvious cause for bleeding or other alternative diagnosis, the patient should be suspected as possibly having a VHF.
Figure 9. Ocular Manifestations in Bolivian Hemorrhagic Fever
Ocular manifestations associated with hemorrhagic fever viruses range from conjunctival injection to subconjunctival hemorrhage, as seen in this patient. Reprinted with permission from Current Science/Current Medicine (Peters CJ, Zaki SR, Rollin PE. Viral hemorrhagic fevers. In: Fekety R, vol ed. Atlas of Infectious Diseases, Volume VIII. Philadelphia, Pa: Churchill, Livingstone; 1997: ).
Marburg Disease
Bolivian Hemorrhagic Fever 49 49

50. VHF - Diagnosis Ancillary testing:
Thrombocytopenia, leukopenia, AST elevation common
Definitive diagnosis requires detection of antigens or antibodies
Testing done at CDC
Do not wait to confirm the diagnosis before notifying the local public health authorities
Diagnosis
Diagnosis is based on the above clinical presentation, and will require a high level index of suspicion.
Thrombocytopenia, leukopenia, aspartate aminotransferase (AST) elevation are common
Definitive diagnosis requires detection of antigens or antibodies; testing done at CDC
Do not wait to confirm the diagnosis before notifying the public health authorities. 50 50

51. VHF - Treatment Supportive care Ribavirin may be useful
Best early in the course of illness
Adults and children: 30 mg/kg IV load (max 2 g)
then 16 mg/kg (max 1g) q6h x 4 days
then 8 mg/kg (max 500 mg) IV q8h for 6 days
Oral dosing regimen is available
Treatment
Supportive care
Ribavirin may be useful for some of the hemorrhagic fever viruses. If available, it can be started empirically (adults and children: 30 mg/kg IV load [max 2 g] then 16 mg/kg [max 1g] q 6h x 4 days, then 8 mg/kg [max 500 mg] IV q 8h for 6 days). An oral dosing regimen is also available.
Pregnant women receive the same treatment as above 51 51

52. VHF - Infection Control
Prophylaxis:
None at this time
Vaccine in primates being tested
Isolation: Key!
Blood and bodily fluids extremely infectious
Liquid-impervious protective coverings, including leg and shoe coverings
Double gloves, Face shields or goggles
N-95 or better respirators
Negative pressure room
Currently no prophylaxis is available. The NIH, however, is currently evaluating a possible vaccine candidate.
Hemorrhagic fever viruses (HFV) are extremely contagious after contact with blood and bodily fluids. Beyond routine contact precautions, personnel should wear liquid impervious protective coverings (including leg and shoe coverings) and use double gloves. Although airborne spread has never been demonstrated the possibility has not been excluded. Personnel should wear N-95 or better respirators. In addition, face shields or goggles should be used to protect the eyes from possible contact with infected materials. Patients should be placed in a negative pressure room if possible. Experts should be contacted for further recommendations. 52 52

53. Emerging Infectious Diseases53 53

54. A Global Epidemic! Pandemic 54
NEAT PHOTO but consider deleting this one and moving the speaker notes to the next slide…
Emerging infectious diseases also cause “natural disasters”. During the 1970’s, “Legionnaires’ Disease” caused numerous deaths in the United States, following an outbreak at an American Legion convention in Philadelphia. More recently, West Nile Virus has spread throughout at least 44 states, also causing fatalities, especially among the elderly. In 2002, more than 4100 cases were reported to the Centers for Disease Control and Prevention. As of late November 2003, that number had more than doubled to over 8500 cases for Both of these figures likely reflect a degree of under-reporting, so the actual number of cases may well be even higher. Although the number of reported deaths due to the virus has remained constant at approximately 200 for 2002 and for 2003, West Nile Virus is still a significant cause of morbidity. Although the virus is not directly communicable from person-to-person, it can be transmitted through blood transfusions or organ transplants. Consequently, the disease has also exacted a significant economic toll due to the introduction of screening and testing methodologies. 54 54

55. Past flu pandemics 1918: “Spanish Flu” 1957: “Asian Flu”
Credit: US National Museum of Health and Medicine
As you can see, the Spanish Flu in 1918 was the most severe of the three pandemics resulting in 20 to 40 million deaths worldwide and 675,000 U.S. deaths. The Asian Flu pandemic resulted in double the usual number of flu season deaths in the US. The Hong Kong Flu pandemic was relatively mild by comparison.
Slide images and figures from online slide set of Barbara Wallace, New York State Department of Health 2005
The swine flu epidemic of 1976 was a difficult public health policy challenge. A very small number of people became sick with a virus (swine H1N1) which looks very much like what was known at the time about the 1918 flu. The reaction was to produce a vaccine as quickly as possible, lest 1918 repeat itself. As it happened, the virus did not transmit very well and the feared epidemic never materialized. However, the vaccine caused some side effects (~1000 cases of guillan bar’e), so the cure turned out to be worse than the disease. However, better to have a vaccine w/ no epidemic than an epidemic with no vaccine.
1918: “Spanish Flu”
1957: “Asian Flu”
1968: “Hong Kong Flu”
A(H1N1)
A(H2N2)
A(H3N2)
20-40 m deaths
675,000 US deaths
1-4 m deaths
70,000 US deaths
1-4 m deaths
34,000 US deaths 55 55

56. Put another way …
In actuality, the 1918 influenza pandemic temporarily lowered the life expectancy in the US by more than 10 years! 56 56

57. Pandemic Influenza www.cdc.gov57 57

58. Pandemic Influenza 58 58

59. Pandemic Influenza Healthcare Workforce
Who is going to show up for work?
The reports, articles and plans are alarming!
Will you? 59 59

60. Containment Limit travel Isolate ill and quarantine exposed
Trace contacts
Curfews & cancel public gatherings
Prophylaxis & treatment
Neuramidase inhibitors ?
Vaccine ? 60 60

61. D: Detection I: Incident Command S: Safety & Security
A: Assess Hazards
S: Support
T: Triage & Treatment
E: Evacuation
R: Recovery 61 61

62. Detection There may not be a “scene” May be hard to detect
Long Incubation period
Symptoms manifest slowly
Non-specific symptoms
Beware of multiple people with similar
Complaints, particularly in the “healthy” population 62 62

63. I: Incident Command D: Detection S: Safety & Security
A: Assess Hazards
S: Support
T: Triage & Treatment
E: Evacuation
R: Recovery 63 63

64. Incident Command Absence of a “scene” if covert
Lead role of law enforcement
Unified command of law enforcement and public health
Special public health emergency powers
Because man-made biological events differ in several key characteristics from these other emergencies, incident command and emergency management procedures must accommodate these differences when responding to the event. These elements include the absence of a scene, the primary role of law enforcement in crisis management, the need for unified command between law enforcement and public health, and the special powers needed for the protection of persons during a state of public health emergency. 64 64

65. Security Hospital ingress and egress Most bioattacks likely covert
Must be able to secure hospital
Most bioattacks likely covert
Patients will come in through ER
ER becomes the “scene”
Most biological attacks are likely to be covert. Patients will come in through ER, and the need for patient decontamination will probably no longer exist. 65 65

66. Suspicious Package Do not open suspicious packages Secure area
Shut off ventilation if possible
Alert appropriate authorities
When someone receives a container with a powder-like substance and a threatening communication, the response should be coordinated among the local hazardous materials (HAZMAT) team, local law enforcement, and public health. HAZMAT, using appropriate personal protection equipment (PPE), should secure the specimen in an appropriate container (triple-bagged in clear, Ziploc bags or a sealed HAZMAT container). 66 66

67. Assessing Hazards Protective isolation & quarantine
Epidemiologic assessment
Environmental assessment
Laboratory diagnosis of ill persons
Role of immunization, prophylaxis and treatment
Little role for decontamination 67 67

68. Personal Protective Equipment
Degree of protection
Controversial
CDC guidelines
Very conservative
N-95 respirators, gloves, fluid-impervious gowns
Better than nothing 68 68

69. Support Initially, local management issue! Local hospital capacity
Local healthcare providers
Is your local community ready?
As with any other disaster, the initial response to a BT event depends on local planning, preparedness and resources. Additional assistance, whether on a state or federal level, requires a minimum of 24 to 72 hours to arrange and deploy once the BT event has been recognized and assistance requested.  
The health care delivery system will probably be totally over-burdened prior to recognition of the BT event. Recognition of the event and the agent are also critical with regard to what type of assistance is required, such as surge capacity for patient care including bed space and health care providers, pharmaceuticals and supplies, or emergency management support for maintaining necessities such as utilities or security.
All requests for support must go through the appropriate channels, such as public health and emergency management agencies, or through executive offices such as mayors and governors. Most state and federal assistance services can be mobilized within 12 to 24 hours after the request has been received and approved. If the BT event takes several days to recognize, support may not arrive until well into the response effort when local resources have been exhausted.
Federal assistance to state or local emergency management counterparts is primarily coordinated through the Federal Emergency Management Agency (FEMA). The newly formed Department of Homeland Security (DHS) operates FEMA, and, in collaboration with other agencies, provides additional public health and medical assistance through two services, the National Medical Disaster Medical System (NDMS) and the Metropolitan Medical Response System (MMRS).
The NDMS consists of teams of professionals with various capabilities such as patient care augmentation (Disaster Medical Assistance Teams [ DMAT]), victim identification and mortuary services (Disaster Mortuary Operational Response Teams [DMORT]), and animal and sanitation support (Veterinary Medical Assistance Teams [VMAT]). The NDMS also has a casualty transportation branch to relocate non-BT patients to off-load hospitals and allow more directed BT effort. MMRSs have been developed in 120 cities by federal funding to coordinate local response efforts, particularly in response to chemical and BT events. They enhance communication and coordination between public health, law enforcement, fire, HAZMAT, EMS, and medical delivery assets on a local basis. 69 69

70. Support Local Hospital Capacity
Coordination & Augmentation
Pre-event planning essential for “surge”
Surge facilities for medical care expansion
Expect being overrun with “worried well”
Involvement of local pharmacies
The health care system in the Untied States is near capacity on a routine basis. Creating surge capacity to accommodate large numbers of additional patients is not available in most communities. Pre-event planning and preparedness is essential to develop local capabilities and to expand health care capacity. The number of beds within a community may be expanded by either optimizing the use of the existing beds, ie, canceling elective surgeries and discharging or transferring non-critical patients, or adding additional beds. Emergency expansions of hospitals may be possible within the facility itself (using cafeterias or auditoriums), or outside the facility (using nearby schools, gymnasiums, hotels, conference centers, or community centers). Each hospital or community should have contingency plans with a designated facility with the appropriate characteristics to be used as a medical expansion facility including utilities, accessibility and parking, refrigeration and storage, and communication (telephones and public address systems). Prepositioned supplies such as stretchers, beds, or cots must also be available for rapid deployment.
During any terrorist or catastrophic event, EDs are at high risk of being overrun with patients. Hospital and community emergency plans should include ways to avoid this. Public information and instructions to potential patients through the media is essential to help direct the flow of patients and help people assess their own risk and need for medical evaluation. During all natural or contrived events, many or most people attempting to obtain care are not directly involved in the event , the “the worried well”.
Attempts to off-load and protect EDs may include neighborhood emergency health centers (NEHC) where people with BT-related problems may be triaged and receive limited medical care, transferred to another care facility, or receive prophylaxis if appropriate. These centers may be staffed by para-professionals and also function as a center for the dissemination of medical information and advice to the public.
Every hospital should have contingency plans to rapidly fill their increased needs during a BT event by having pre-arranged agreements with pharmaceutical wholesalers and suppliers. All wholesalers can provide pharmaceuticals for multiple hospitals and clients following pre-event discussions of prioritization and use of available stores during an event. This may also include agreements with local pharmacies to consolidate supplies of medications during an emergency. 70 70

71. Support: Strategic National Stockpile
Pre-positioned material managed by CDC and DHS
Medications, antidotes, vaccines, PPE, equipment,et al.
12 hour Push Packages
Vendor managed inventory
Local coordination of receipt critical
Obviously following an act of terrorism that targeted the civilians in the United States, local and state medical resources could quickly be overwhelmed. In order to address this problem, the Department of Health and Human Services (DHHS) and the CDC developed the National Pharmaceutical Stockpile. In 2003 this program was renamed the SNS and was put under joint management of the by the Department of Homeland Security (DHS) and DHHS.
The SNS is a national repository of antibiotics, chemical antidotes, antitoxins, life-support medications, vaccines, IV administration, PPE, airway maintenance supplies, and medical/surgical items. It is designed to supplement and re-supply state and local public health agencies in the event of a national emergency anywhere and at anytime within the U.S. or its territories.
The first line of support lies within the immediate response 12-hour Push Packages. Each package is designed to respond during the early hours of an ill defined threat. These “Push Packages” can be delivered within 12 hours to anywhere in the United States. An average SNS delivery consists of approximately 50 tons of supplies, which are color coded and organized for easy inventory and distribution.
Delivery is made to the nearest FedEx hub airport or trucked in if necessary, or both. A predesignated storage facility measuring at least 5000 square feet is required for delivery and staging. Local licensed pharmacists are required to receive the shipment and direct the distribution of supplies. The medications are delivered in both individual patient packages and bulk quantities. Both automated and manual medication packaging devices are included with the SNS as well as the attendant bags, bottles and labels. In addition to the pharmacists, up to 300 other personnel are needed to handle the supplies. A small team of CDC advisors (Technical Advisory Response Team [TARU]) is deployed with each lot to assist with inventory and organization. The medical decision-making regarding use of the supplies, however, remains with the local response leadership.
If the incident requires additional pharmaceuticals and/or medical supplies, follow-on vendor managed inventory (VMI) supplies will be shipped to arrive within 24 to 36 hours. If the agent is well defined, VMI can be tailored to provide pharmaceuticals, supplies and/or products specific to the suspected or confirmed agent(s). In this case, the VMI could act as the first option for immediate response from the SNS. 71 71

72. Triage Three types of patients: (1). Ill and need definitive treatment
(2). Exposed but not ill: may need prophylaxis and quarantine
(3). Not exposed: need reassurance
Difficult to distinguish between groups 2 & 3!
Once a release is known to have occurred, special triage stations should be established to distinguish 3 categories of patients:
Ill: need definitive treatment
Exposed but not ill: may need prophylaxis
Not exposed: need reassurance
Until definitive epidemiologic studies define the actual risk factors, it is difficult to distinguish between groups 2 and 3.
In the event of an overt release, initial management is as for a chemical attack, including the need for patient decontamination (in this case with soap and water) 72 72

73. Evacuation Dedicated treatment facilities Isolation of patients
Surge capacity implications
Hospital becomes a “scene” 73 73

74. Recovery Law enforcement Evidence, apprehension, prosecution,...
Public health
Stop spread, identify source, treatment options,...
Mental health
Wide-spread panic, “worried-well”, responders,...
Environmental health
Viability of weaponized release, “nature” effects, soiled materials,...
For law enforcement officials, full recovery follows the apprehension and successful criminal prosecution of the perpetrator. Other response agencies (public health, mental health) need to respect and assist in law enforcement’s investigation when called upon to do so. Such assistance may include preservation of a chain-of-custody and other actions to protect evidence for subsequent prosecution. Law enforcement activities may have a direct impact on the public’s health; apprehension of the perpetrator may halt the ongoing release of a biological agent into the environment.
One of public health’s primary responsibilities in the wake of a biological event is to halt the spread of disease and assure appropriate medical treatment of those exposed. Recovery efforts need to be focused on identifying the source and interrupting the release of the agent.
Providing for the mental health needs of disaster victims, their families, and emergency response workers is an essential function of emergency management. Mental health issues following biological events and other forms of terrorism may differ from those seen in other disasters. Psychological responses following a biological terrorist attack include anger, panic, fear of contagion, scapegoating, social isolation, demoralization, and loss of faith in social institutions. A critical first step is an effective risk communications plan, with the identification of credible and trusted spokespersons who can provide accurate and frequent assessments of what is known and what is not known as events unfold.  
Medical personnel must anticipate that a biological attack may produce contagious somatization—breathing difficulties, tremors, sweating, feelings of anxiety, and labile moods. Symptoms such as these may compel the worried well to seek care at health care facilities, thereby reducing the capacity to provide care for legitimate victims. Thus, mental health services need to be fully integrated into the triage function performed at NEHCs. Medical responders need to be able to recognize symptoms of anxiety, depression, and dissociation.
Acute stress disorder may be common among both victims and responders. With appropriate treatment, however, including emphasis on the normal recovery process—talking to others, getting rest and respite, and returning to normal routines—recovery may be facilitated.
Under most circumstances where a biological event is involved environmental health issues are not particularly pronounced or challenging. Most bacteria and viruses that might be used as biological agents have limited viability in the natural environment; ultraviolet light, desiccation, and other natural forces limit the risk of human exposure from the environment, particularly with the passage of time. Existing hospital procedures for handing soiled clothing and linen and disinfecting rooms and treatment surfaces should be sufficient. Similarly, existing procedures for processing fatalities should be enough to protect those engaged in such tasks. Limited data on the airborne release of anthrax from a former Soviet biological weapons plant suggested that the risk of illness from secondary exposure (eg, re-aerosolization following initial release and deposition on the ground and other surfaces) was minimal. Recognition of new methods of pathogen delivery, such as letters containing dry anthrax spores, as well as an appreciation for their efficient and thorough contamination of the environment, has led to a revised consensus that for circumstances involving anthrax spores, environmental assessment should be conducted by experts on an individual case-by-case basis. 74 74

75. Summary
Now you can:
Describe the difference between biological events and bioterrorism (BT)
Discuss public health BT surveillance
Identify the CDC BT Category A agents
Identify emerging infectious diseases
Compare and contrast BT and other CBRNE WMD utilizing the DISASTER paradigm 75 75

76. Questions? 76 76