BIODEFENCE

1
??? ???? ?????? ??????
BIODEFENCE Epidemiology of Plague Shahid Beheshti
University of medical sciences, 2005 By Hatami
H. MD. MPH
2
??? ? ????? ? ????? ??????
? ? ??????????? ?????? ? ????(OCCURRENCE)

• 1- ????? ? ????? ???????
• 2 ???? ?? ????? ?????????

? ? ??????? ? ?????
3
1- Definition

• A special zoonosis involving rodents and their
  fleas
• Transmits to various animals and to human

4
Importance

• One of three WHO quarantinable diseases
• Estimated 200 million deaths recorded
• Three prior pandemics
• Justinian 541 AD
• Black Death 1346
• China 1855

5
Importance

• Naturally occurring human outbreaks parallel and
  follow epizootics
• BT event may also spawn sylvatic plague
• Following disasters
• Disruption of rat habitats
• Transport of disease
• through rat relocation

6
Bioweapon Potential

• One of top 6 agents identified by CDC (category
  A)
• Known attempted uses
• In kaffa
• Japanese (Unit 731) WWII infected fleas released
  over China
• Weapons programs
• U.S. terminated 1970
• Russia unknown

7
Bioweapon Potential

• Estimated Effect
• Aerosol release 50kg Y. pestis over city of 5
  million people
• 150,000 infected
• 36,000 die

8
Bioweapon Potential

• Delivery Mechanism
• Aerosol
• Bioweapons programs developed techniques to
  aerosolize plague directly
• Pneumonic form would be expected
• Proven infectivity of primates

9
Factors suggesting BT aerosol

• Several cases of primary pneumonic (no or few
  bubonic)
• Peak in number of previously healthy persons with
  cough, fever, death
• Many with GI symptoms
• Occurs in non-endemic area

10
Factors suggesting BT aerosol

• Epidemic of severe/fatal pneumonia (hemoptysis)
• Symptoms 1-6 days after exposure
• Occurs in persons without risk factors

11
2- Etiologic agent

• Taxonomy
• Family Enterobacteriaceae
• 11 Yersinia species 3 human
  pathogens
• Y. pestis
• Y. pseudotuberculosis
• Y. enterocolitica

12
Microbiology

• Staining
• Gram negative coccobacillus
• Giemsa, Wright, Wayson stains bipolar staining

13
Environmental Survival

• Requires host
• Does not survive in environment well
• Can live weeks in water, moist soil
• Lives months/years at just above freezing
  temperature
• Lives only 15 minutes in 55 C
• Lives in dry sputum, corpses, flea feces
• Inactivated by sunlight in a few hours

14
Pathogenesis

• Highly virulent and invasive
• Four routes human disease
• Flea-bite (most common)
• Handling infected animals- skin contact, scratch,
  bite
• Inhalation from humans or animals
• Ingesting infected meat

15
Pathogenesis

• Intracellular organism
• Survives in monocytes/macrophages
• Inhalation (pneumonic form)
• Deposition into alveoli
• Classic lobular pneumonia
• Resulting manifestation
• liquefaction necrosis, residual scarring

16
? ? ??????????? ?????? ? ???? ?????
1 ???? ?????? (Incubation period) 2 ???
?????(Natural course) 3 ??????
?????????(Geographical distribution) 4 ????
?????(Timeline trend) 5 ????? ??? ???? ??? ?
?????? ??????? 6 ????? ????? ?????
?????(Predisposing factors) 7 ?????? ?
??????(Susceptibility Resistance) 8 ?????
???? ??? ??????(Secondary attack rate) 9 ????
?????? ? ???? ?????? ????? (Mode of transmission
period of communicability)
17
1 ? ???? ??????

• Incubation Period
• 1-7 days
• Longer in immunized individuals
• For primary pneumonia, 1-4 days
• Ref. Control of communicable diseases

18
Clinical Features
2 ? ??? ?????

• Three types of Disease
• Bubonic
• Septicemic
• Pneumonic

19
Clinical Features

• Bubonic
• Classic
• Predominates )84(
• Usually from bite of infectious flea
• Contact ingestion of infected animals

20
Clinical Features

• Buboes
• Enlarged tender lymph nodes
• Usually unilateral
• Usually inguinal/femoral in adults
• Cervical/submaxillary more common in age lt 10

Image Armstrong Cohen
21
Clinical Features

• Bubonic
• Mortality
• 40-60 untreated, lt5 treated
• Overall case fatality 14 in U.S.
• Usually from delayed Dx and Rx
• Complications
• Often develop bacteremia
• Some develop
• Septicemia (secondary septicemic plague)
• Pneumonic (secondary pneumonic plague)
• meningitis

22
Clinical Features

• Septicemic
• Historically 12
• Secondary
• if complication of bubonic
• Primary
• if no buboes detected

23
Clinical Features

• Septicemic
• Similar to other gram-negative sepsis
• Mortality
• Overall 50
• gt 90 untreated
• Usually from late diagnosis and Rx

24
Clinical Features

• Pnuemonic
• Approx. 2 all plague are primary pneumonic
• Secondary
• if preceding bubonic (most cases) or septicemic

25
Clinical Features

• Pneumonic
• Primary if result of droplet inhalation
• From other pneumonic plague patients or infected
  animals
• From expected if aerosolized as a bioweapon
• Extremely infectious via droplets and purulent
  sputum

26
Clinical Features

• Pneumonic
• Mortality
• Nearly 100 untreated or if delayed gt 24 hrs
  after symptom onset
• High despite treatment
• Overall case fatality 57 in U.S.

27
(No Transcript)
28
Clinical Features

• In BT event pneumonic form most likely
• Pneumonic
• incubation 1-6 days for primary
• Initialacute flu-like , myalgia, malaise
• Often prominent GI , abd pain
• Severe pneumonia
• Within 24hr of onset
• Cough, hemoptysis
• Progresses to cyanosis, stridor
• Death usually occurs 2-4 days after exposure

29
Clinical Features

• Immunity
• Several days after infection
• lt5 never
• Transient, not life-long immunity after surviving
  
• May not protect against a large inoculum
• Antibody levels normalize in months-years

30
2 ? ??? ????? (????)

• ????? ????? ???? ????? (??? ????????)
• ????? ????? ???
• ????? ????? ????
• ????? ????? ?????? ????????
• ??? ???? ?????? ?? ????? ? ???? ?????
• ????? ???????? ? ????????

31
3 ? ?????? ?????????
32
Geographic distribution

• Globally
• Approximately 1500 cases/year since 1965
• 25 countries reported cases
• gt 50 Eastern, S. Africa,
• U.S.
• 390 cases/year reported 1947-96
• Southwest region of U.S. endemic

33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36
4 ? ???? ?????

• ?????? ?? ?(Pandemics)
• ?????? ?? ?(Epidemics)
• ????? ?? ? (Outbreaks)
• ????? ????? ? (Duration)
• ????? ???? ?(Seasonality)

37
5 ? ????? ??? ??? ? ??? ? ?????? ???????

• ????? ?? ?? ????? ???? ? ???? ? ????? ?? ????? ?
  ???? ????? ? ???? ? ???? ? ?????? ???? ??? ?
  ????? ??? ? ???
• ????? ??? ?? ????? ?????
• ??? ? ?????? ??????? ?

38
6 ? ????? ????? ????? ?????

• ????? ?????? ? ??????
• ????? ???? ???? ??? ????? ? ?????? ?? ?????????
  ??????? ????? ? ???? ??????? ???? ????? ?????
• ????? ??? ?????
• ??? ? ?? ???????

39
Risk factors

• Close contact with case
• Contact with infected animal
• Living or recent travel in endemic area
• Residing in crowded conditions
• Cool, wet weather
• Exposure to a known intentional release

40
7 ? ?????? ? ?????? ?? ????? ??????

• ?????? ?????
• ?????? ??????? ??? ?? ??????
• ?????? ??????? ??? ?? ???????????

41
8 ? ????? ????? ??????

• Pneumonic plague may be highly communicable under
  appropriate climatic conditions

42
9 ? ????? ? ????? ? ???? ?????? ?????? ? ????
?????? ????? ?????
43
Transmission

• Mostly endemic sylvatic plague with sporadic
  cases
• Person to person spread
• Higher risk in
• Overcrowding,
• Indoor contacts,
• Cold/wet weather
• Fleas may remain infective for months

44
Transmission
Bioterrorism
45
Period of communicability

• Duration of isolation
• 2 days after initiating antibiotics and
  clinically improved
• After sputum cultures negative

46
Reservoir

• Wild rodents
• Rabies hares
• Wild carnivores
• Domestic cats

47
? ? ??????? ? ????? ?????

• Primary Prevention
• Prevention of disease in well individuals
• Secondary Prevention
• Identification and intervention in early stages
  of disease
• Tertiary Prevention
• Prevention of further deterioration, reduction in
  complications

48
1 ? ??????? ??? ????
1 ? ?????? ????????? ??????? ???? 2 ? ??? ??????
?????? (????? ????? ????? ?????? . . . 3 ?
?????????? ?? ???????? (????? ???????) ?
?????????????
49
Prevention

• Vaccination
• - Bubonic only
• Killed virulent strain
• No longer commercially available
• Series
• 3 primary (0 , 3 mo and 6 mo later)
• boosters at 6 mo intervals

50
Prevention

• Vaccination
• Indications
• Lab workers
• Military personnel stationed in endemic areas
• Efficacy
• Based on WWII (0 cases) and Vietnam (3 cases)
  troops
• Protects vs. bubonic only, not pneumonic

51
Infection Control

• Respiratory Droplet Precautions
• Wear mask, gown, gloves, eye protection
• Suspected cases - isolate
• Immediately respiratory (even for bubonic)
• Avoid unnecessary close contact 1st 48 hrs of abx
• Duration
• 2 days after initiating antibiotics and
  clinically improved
• After sputum cultures negative

52
Infection Control

• Respiratory Droplet Precautions
• Mask during transport
• Can cohort if not enough room
• Contacts consider isolation
• Recommended for those receiving PEP
• During 1st 48 hrs of Rx
• Not recommended for those refusing PEP
• but still observe 7 days

53
Infection Control

• Standard Precautions
• Successfully treated cases after 48hr of abx
• Laboratory safety
• Alert lab if suspected
• BSL-2 for normal procedures
• BSL-3 if hi risk aerosolizing or resistant
  strains

54
Infection Control

• Corpses
• Standard strict precautions by trained personnel
• Transport same as live patient
• Avoid aerosolizing procedures or use HEPA filters
  and negative pressure room

55
Infection Control

• Outbreak measures
• Establish source
• Define geographical boundaries
• Establish active surveillance
• Laboratory confirmation of cases
• Isolation of pneumonic cases
• Rapid treatment of cases and contacts
• Flea and rodent control

56
Infection Control

• National control programs
• Surveillance
• Early diagnosis, treatment isolation of cases
• Environmental sanitation exposure avoidance
• Public education

57
Decontamination

• Environment
• Aerosol dispersed within an hour fragile
• No evidence residual bacteria are a threat
• No environmental decon. indicated
• May need surveillance measures for rodents/fleas
  in area

58
Decontamination

• Patient rooms
• Usual cleaning
• Use standard precautions
• Disinfect contaminated linens
• Standard disinfectants

59
Post-exposure Prophylaxis

• Also for mass causalities
• For all asymptomatic contacts of suspected
  untreated pneumonic cases
• Contact within last 6 days
• Untreated pneumonic lt48hr approp treatment
• Those within 2 meters of case
• Household, hospital contacts
• Those who might have been exposed to initial
  aerosol
• Seek out homeless, mental handicaps, homebound

60
Post-exposure Prophylaxis

• Antibiotics
• 1st choices
• Tetracyclines
• Doxycycline
• 100 po bid adults and kids gt45 kg
• 2.2 mg/kg po bid for kids lt45 kg
• Tetracycline equivalent dosages
• Fluoroquinolones
• Ciprofloxacin
• 500 mg po bid for adults
• 20 mg/kg po bid (max 1g/day) for kids
• Others at equivalent dosages

61
Post-exposure Prophylaxis

• Alternatives
• Chloramphenical 25 mg/kg po qid
• Not in kids lt2yo
• For pregnant breastfeeding women
• Same as adults above but no tetracycline
• Doxycycline may be used
• Duration
• 7 days since last exposure PEP
• 10 days for mass casualties

62
2 ? ??????? ??? ????
1 ? ????? ????? 2 ? ????? ?? ???? 3 ? ???? ??
????? ?? ????? ??????? ??? ???? ? ????
63
Diagnosis

• No rapid tests available treat first
• Report suspected cases to local health dept if no
  risk factor for naturally occurring disease
• Send out samples if not done in hospital
• Obtain specimens as indicated
• Blood attempt 4 samples q30 min
• Bubo aspirate (inject 1-2cc saline and aspirate
  with 20 Ga needle)
• Sputum
• CSF

64
Diagnosis

• CXR
• Inoculate on/in infusion broth, blood agar,
  McConkey agar
• Biochemical profiles if automated system has
  capacity to detect
• Stains Gram and Waysons or Giemsa
• DFA testing
• Acute serum for F1 antibody
• CDC sample for bacteriophage lysis

65
Treatment

• Start immediately upon suspicion of diagnosis
• Delay gt1day after symptoms usually fatal

66
Treatment

• Antibiotics
• General
• Contained casualties IV
• Mass casualties po equivalent, same as
  post-exposure prophylaxis
• Also need intensive supportive care
• Ventilation
• Pressors usually not needed
• Who to treat
• Suspected cases
• Index
• If suspected release anyone with fever, cough

67
Treatment

• Special populations
• Children
• Same as adults but try avoid TCN if lt8yo
• No chloramphenicol for lt2 yo (grey baby syndrome)
• Pregnant women
• Try to avoid streptomycin
• 1st choice gentamicin, same adult dose
• 2nd choice doxy, same adult dose
• 3rd choice cipro, same adult dose
• Breastfeeding women
• Same recommendations as pregnant
• Immunosuppressed no different than competent

68
Treatment

• Antibiotics for contained casualties
• (For mass casualties, same as PEP)
• 1st choices
• Streptomycin - FDA-approved
• 30 mg/kg IM divided q8-12 kids (max 2g/day)
• 1g IM bid adult
• bacteriocidal
• gentamicin as effective, more avail, qd dosing
• 5mg/kg iv qd, w/levels or load 2mg/kg then
  1.7mg/kg q8
• 2.5mg/kg im/iv q8h kids (q12hr for lt1wk or
  premature)

69
Treatment

• 2nd choices
• tetracyclines - as good in vitro, good human data
• doxycycline
• single 200mg iv loading dose (some sources)
• 100mg iv bid or 200 mg iv qd adults kids gt45kg
• 2.2mg/kg iv q12hr (max 200mg) kids lt45kg
• Better absorption, distribution, half-life than
  TCN
• 1st choice po therapy for mass casualties
• tetracycline
• 500 mg po qid adults
• 6.25-12.5 mg/kg po qid kids gt9yo

70
Treatment

• 2nd choices
• Fluoroquinolonesbetter in vitro, no human data
• ciprofloxacin
• 400 mg iv q12hr adults
• 15 mg/kg iv q12hr kids (max 1g/day)
• Levofloxacin
• Ofloxacin
• Chloramphenicol
• 1st choice for meningitis /- aminoglycoside
• Crosses blood-brain barrier
• 25mg/kg iv q6hr adults kids, keep level 5-20
  µg/ml
• Avoid in kids lt2 yo (grey baby syndrome)

71
Treatment

• 2nd choices
• Alternatives sulfonamides
• If other antibiotics not available
• Ineffective for pneumonic
• TMP-SMX
• Generally ineffective
• ?-lactams, rifampin, aztreonam, macrolides

72
Treatment

• Antibiotic resistance rare
• May be expected in BT scenario (engineered
  agents)

73
Treatment

• Switch to po when improved, tolerates
• Usual response
• Bubonic improved in 2-3d, afebrile 2-5d
• Duration 10-14 days or 3 days after afebrile,
  improving
• Supportive care
• Volume status maintenance
• Hemodynamic monitoring
• pressors not usually needed
• Support of multiorgan failure

74
Treatment

• Bubo care
• Usually recedes with antibiotics
• Rarely become fluctuant/abscessed
• Unnecessary I D increases contacts risks

75
????? ?????
1 ? ?????? ?? ????? ? ????? 2 ? ??? ??????
?????? 3 ? ??? ????? ????
76
????? ?????

• 1 ? ?????? ?? ?????
• ??????? ??????? ? ?????? ??
• ?????? ???? ??????? ??
• ????? ???? ?????? ??
• ????? ???? ?????? ?? ???????
• ????? ???? ????? ??
• ??????? ????? ? ????
• ????? ????? ??

77
????? ?????

• 2 ? ??? ?????? ??????
• ???????? ?????? ? ?????????
• ??? ??? ? . . .
• ????? ????? ???? . . .

78
????? ?????

• 3 ? ??? ????? ????
• ???????? ?????
• ???????? ?????
• ?????????????