Children, Terrorism and Biological or Chemical Weapons, 2005

1
Children, Terrorism and Biological or Chemical
Weapons, 2005

• Fred M. Henretig, MD
• Childrens Hospital of Philadelphia
• Division of Pediatric Emergency Medicine
• Poison Control Center, Philadelphia

2
Before 1993 Pediatric
Mass Casualty Disasters

• traditional disaster planning, committees,
  drills, but threat distant
• then
• World Trade Center, 1993 1042
  injured, 6 deaths
• Oklahoma City, 1995
  750 injured, 167 deaths ( 19 children)

3
(No Transcript)
4
Children collateral damage
5
A New Spectre Biological and
Chemical Terrorism

• Rajneeshee salmonella attack, The Dalles, OR 1984
• Gulf War, 1990-91
• Tokyo subway sarin attack, 1995

6
And then came Sept 11th, and Oct and
Nov, 2001
7
(No Transcript)
8
(No Transcript)
9
Biological terrorism not just your average
epidemic

• intent to cause mass casualties
• more virulent agents
• delayed dx due to exotic diseases
• potential greater risk to physicians
• mass hysteria, many worried well
• more compressed time frame of outbreak
• more respiratory forms of disease
• infected, dying animals

10
Biological and Chemical Terrorism Potential
Pediatric Vulnerabilities

• physiologic
• developmental
• psychologic
• EMS deficiencies re pediatric mass casualties

11
Physiologic Factors - Respiratory

• closer to the ground
• increased relative minute
• ventilation

12
Physiologic Factors - Dermal

• thinner, more permeable skin
• increased BSA / mass ratio

13
Physiologic factors - Immunologic / Anatomic

• immunologic immaturity
• more permeable
• blood-brain barrier

14
Developmental Factors

• less capacity to escape,
• take evasive actions

15
Psychologic Factors

• less coping skills with
• personal or witnessed injuries
• increased anxiety with
• incidents, hoaxes, media coverage

16
EMS Factors

• (?) less capacity to cope with large influx of
  critical pediatric patients
• (?) procedural challenges, esp garbed in PPE
• less reliance on routine transfer protocols
• limited pediatric bed expansion capability in NDMS

17
Imaginemultiple pediatric patients presenting
simultaneously, requiring immediate
treatment, with unfamiliar, intravenous
medications, by first responders in
PPE for rarely encountered conditions
18
Biological Agents-Pediatric issues

• different, more severe disease course?
• less familiarity with antibiotics, eg cipro, doxy
  (but probably not so much of an issue any more!)
  
• most vaccines not approved in kids
• no child immunized to smallpox

19
Major Biologic Agent Threats

• Anthrax
• Smallpox
• Plague
• Botulinum toxin
• Tularemia
• Viral hemorrhagic fever

20
Biological Agents and Children 2005

• Anthrax angst
• Smallpox redux
• Botulism beware
• Diagnostic challenges

21
Anthrax

• Greatest threat - WHO estimates 50 kg release to
  500,000 population city 125,000 infections with
  95,000 fatalities
• weaponized by US (stockpiles destroyed 1969),
  USSR and Iraq
• accident at Sverdlovsk in 1979 caused 66 deaths
• October, 2001...
• Gram sporulating rod, Bacillus anthracis, very
  hardy spore form, easily aerosolized, ideal size
  (2-6 microns) for inhalational infection
• Cutaneous, GI and inhalational forms

22
(No Transcript)
23
Anthrax - inhalational

• Incubation 1-6 days flu-like illness for 1-2 d
  rapid deterioration with dyspnea, cyanosis,
  shock, sepsis, meningitis
• CXR widened mediastinum, /- pleural effusions,
  pulmonary infiltrates
• blood culture for G rods (likely considered
  contaminant initially, at least pre-Oct 2001)
• Death (historically) in 95 in which rx delayed
  48 hrs or more ( 5/11 in Oct 2001)

24
(No Transcript)
25
(No Transcript)
26
Anthrax - inhalational

• Rx ciprofloxacin (adults 400 mg IV q12h, peds
  20-30 mg/kg/d in q12h doses) or doxycycline
  (adults 100 mg IV q12h, peds 2.2 mg/kg IV q12h)
  1 or 2 additional abx ( eg rifampin, vancomycin,
  pencillin, clindamycin, ) recommended by CDC in
  Fall, 2001
• Prophy cipro or doxy ( amox for children, if
  susceptible) PO for 60 days ( or longer!)
• ? vaccine
• Little risk to HCWs

27
Anthrax- cutaneous

• less anticipated in BT context before Oct 2001
• can look like a brown recluse spider bite!
• Papule?vesicle?ulcer
• ?black eschar
• marked edema
• fever, but relatively painless
• much lower morbidity,
• mortality lt 1 with rx

28
Pediatric Anthrax Patient, Oct 2001

• 7 month old son of ABC News employee
• Possible infected insect bite ----gtbrown recluse
  spider bite
• developed hemolysis, thrombocytopenia, renal
  insufficiency
• particular vulnerablity of infancy ?

29
Anthrax 2005

• Vaccine developments, new plasmid DNA technology
• (Proc Natl Acad Sci U S A. 200410113601-6)
• Anthrax vs Flu both share fever, cough, but
  anthrax more neuro ( dizziness, confusion) and
  GI ( n/v), less sore throat/rhinorrhea than flu
• ( Ann Int Med 2003139337-345)
• Decision analysis, pts potentially exposed if
  rapid flu test is -, consider empiric rx pending
  BC
• (Ann Emerg Med 200443318-328)
• Rapid 1-hr serology testing
• ( JAMA 2004 292 30)

30
Smallpox

• Last endemic case in Somalia, 1977
• only known stockpiles at CDC, Atlanta,
• and Koltsovo, Russia
• ? rogue nations, disaffected former USSR
  scientists, genetically engineered viruses

31
Smallpox

• Population no longer vaccinated, therapy lacking,
  extremely contagious
• incubation 7-17 days, permitting wide dispersal
  of disease by exposed persons before illness
  manifests
• 2-4 days of fever, malaise, rigors, vomiting,
  headache, backache
• classic exanthem macules progressing to papules,
  then pustules, starting face and extremities,
  spreading centrally to trunk, all in similar
  stage
• visceral involvement, death in 30

32
(No Transcript)
33
Smallpox

• all children unvaccinated
• potential increased risk for vaccine
  complications
• autoinoculation
• eczema vaccinatum
• encephalitis ( higher in primary vaccinees)
• thus, CHOP Spring 2003 (almost) no pre-event
  employee vaccinations

34
(No Transcript)
35
(No Transcript)
36
PROGRESSIVE VACCINIA Note that the lesions have
no inflammation, and progress in size
without limitation. Child had severe combined
immunodeficiency (SCID) and despite rigorous and
extensive antibody and antiviral chemotherapy,
died with overwhelming viremia.
37
(No Transcript)
38
Smallpox 2005

• Vaccine vexation!
• Adverse effects myopericarditis
  (Am J Epidemiol. 2004160642-51)
• Progressive vaccinia- benefits of topical
  cidofovir
  (J Infect Dis.
  20041901132-9)
• Antiviral therapy po or aerosol cidofovir
  (J Antimicrob Chemother. 2004541-5)
• Recognition on-going studies of CDC approach

39
Botulism

• toxin formed by Clostridium botulinum, an
  anaerobic spore-forming Gram bacillus
• most toxic substance known, LD 50 of 0.001
  mcg/kg
• prevents pre-synaptic release of acetylcholine
  leading to flaccid paralysis and autonomic
  dysfunction
• Natural disease food poisoning, wound botulism,
  and intestinal botulism ( more to follow)
• Terrorist agent likely aerosol of purified toxin

40
Botulism

• latency of 1 to several days, descending
  paralysis starting with bulbar palsies,
  ptosis, blurred vision
• dry mucous membranes, mydriasis, absence
• of fasciculations help to distinguish from
  nerve agent poisoning

41
(No Transcript)
42
Botulism

• Rx questionable efficacy of antitoxins
• possible use of human botulinum immune globulin
  (currently under investigation for infant
  botulism)

43
Case Presentation, May 2005

• 5 mo baby
• CC
• Looks weak
• not eating as much
• HPI past few days
• poor nursing
• Decreased diapers
• PMH negative

44
Physical exam

• VS afebrile, wnl
• Alert, active spontaneous movements
• HEENT wnl
• Lungs, heart wnl
• Abd wnl
• Neuro mild head lag, slight slipping thru hands
  when lifted under his arms, /- nl DTRs

45
Hospital Course

• Over 2 days develops more drooling
• More floppy
• Weak gag
• Ptosis
• Sluggish pupils
• Transfer to ICU and rx with BIG
• Positive stool for botulinum toxin!

46
Infant Botulism Syndrome

• Acquired Clinical Syndrome in Infancy
• Constipation
• Descending weakness
• Poor feeding
• Weak cry
• Bulbar involvement

47
Infant Botulism Signs

• Note
• Ptosis
• Disconjugate gaze
• Expressionless face
• Slack jaw
• Arm neck hypotonia
• Courtesy Stephen Arnon
• California Department of Heealth Services

48
Infant Botulism Epidemiology

• Age
• Infants lt 6 months
• Geography
• 90 of reported cases in North America
• Incidence DEgtUTgtCAgtPA
• Risk Factors?
• Construction, honey

49
Infant Botulism Etiology

• Ingestion of Clostridium botulinum spores.
• -soil, honey, etc.
• Intestinal colonization w/ C. botulinum
• (note differs from classic botulism)
• Elaboration of botulinum toxin.

50
Clostridium botulinum

• Gram positive
• Spore forming
• Anaerobic
• Toxinogenic

51
Botulinum Toxin-simple

• 7 distinct toxins (A thru G)
• Toxin types A and B most common
• Perhaps most potent toxin known
• Action
• Inhibits release of presynaptic Ach vesicles

52
Bot toxin-advanced

• Arnon et al
• JAMA 20012851059-1070

53
Infant Botulism Diagnosis

• Clinical diagnosis
• Characteristic EMG
• BSAP (brief, small, abundant potentials)
• Identification of C. botulinum organisms or
  toxin!!!

54
Infant Botulism Treatment

• Supportive Care
• -protect airway and support ventilation
• -nutritional management
• -avoid antibiotics (esp. aminoglycosides)
• Specific Treatment
• Human derived botulinum antitoxin

55
Infant Botulism B.I.G.

• Botulism Immune Globulin
• Purified IgG
• Derived from persons immunized with
• pentavalent botulinum toxoid
• Active against toxins ABCDE

56
Infant Botulism B.I.G. Therapy

• Expensive, but...
• ? hospital stay (5.5 to 2.5 weeks)
• ? medical expense
• ? mechanical ventilation
• ? tube feeding

57
Bioterrorism approach to diagnosis-1

• Public health initiatives, e.g.
• Syndromic surveillance
• EDs
• HMOs
• Pharmacies, etc
• Can such systems enhance early discovery of
  illness clusters, with resultant epidemic
  mitigation ? (JAMA 2003 290596-8)
• Still need smart clinicians!

58
Bioterrorism approach to diagnosis-2

• 3 primary syndromes, subacute onset, febrile
• Respiratory
• Anthrax, inhalational
• Plague, pneumonic
• Tularemia, pneumonic
• Neurologic
• Botulism ( afebrile)
• Dermataologic
• Anthrax, cutaneous
• Smallpox
• Plague, septicemic (J Pediatr 2002
  141311-326
• Viral hemorrhagic fevers Emerg Med Clin NA
  200220351-364)

59
(No Transcript)
60
Summary Pediatric Issues in Biological and
Chemical Terrorism

• children- the most vulnerable of potential
  victims
• unique challenges at individual, hospital and
  societal levels
• specific R D needs
• pediatric community can rise to this occasion!