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Lecture organization
Some Rickettsiae and
spirochetes are zoonoses Which lecture covers
them? Rickettsieae and
spirochetes orZoonoses?
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Which topics, which lectures
Rickettsiae &
spirochetes
Rocky MountainSpotted Fever
Rickettsial
biology Rickettsioses
Lyme
Zoonoses
Tick biology
Other tickborne
diseases
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Why Rocky Mountain
Spotted Fever? Prototype rickettsiosis
Main reason for deaths?
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Etiology: Invertebrates
1. Rickettsia rickettsiae
2. Ticks (tolerate infection) Dermacentor andersonii,
D. variabilis (hard)
Transstadial, transovarialtransmission
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Etiology: Vertebrates
3. Reservoir
Small rodents (squirrels)
Tolerate infection4. Humans
Intruders into wildlifecycle
Dead-end hosts
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Etiology
Microbe R. rickettsii
Vector Tick
Reservoir Rodents
Host Intruder
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Rocky Mountain Spotted Fever,
4 dots/case, US, 1999
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Rocky Mountain Spotted Fever,
Monthly Cases, US, 1999
0
25
50
75
100
125
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
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Rocky Mountain Spotted Fever,
cases/100,000, by age, US, 1999
0
0.1
0.2
64
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Person
Outdoor activity
Peak age 5-9
Mortality highest
in elderly
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Rocky Mountain Spotted Fever,
cases/100,000 per year, US
0
0.2
0.4
0.6
1955 1965 1975 1985 1995
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Development of illness
Inoculation
Rickettsemia Endothelial localization
Vasculitis
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Clinical recognition
Rash
Fever
Headache
Other
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Fever and headache
Fever
102 to 105 degrees
2 to 3 weeks without
treatment Headache: severe
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Clinical recognition
Rash
Fever Headache
Other
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Clinical recognition
Rash
Fever Headache
Other
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Laboratory diagnosis
Skin biopsy:immunofluorescent stain
SerologyWeil-Felix archaicImmunofluorescent
antibody No growth on routine culture
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Prevention
Vector control impractical
Vaccine unavailable So . . . caution outdoors
Long clothing
Skin inspection
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Rocky Mountain Spotted Fever
Physician suspicion crucial
R. rickettsii, ticks
Not just Rockies Vasculitis
Rash, fever, headache Doxycycline, look for ticks
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Rickettsiae & spirochetes
Rocky Mountain Spotted
Fever
Rickettsial biology
Other rickettsioses
Spirochetes
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Rickettsial biology:
Bacteria . . . or viruses? Antibacterials
Cell membrane
DNA and RNA
Metabolism
Fission
Most need
host cells
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V C M R B
Lives free 0 0 + +/- +Antibiotic 0 + + + +
Rigid wall +/- +/- 0 + +DNA and RNA 0 + + + +
Makes ATP 0 0 + + +Ribosomes 0 + + + +
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OrderRickettsiales
Family Rickettsiaceae
Tribe Rickettsiae
Genus Rickettsia
Genus Coxiella
Genus Rochalimaea
Family Bartonellaceae
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RickettsiaEhrlichia
Bartonella
Coxiella
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Rickettsial groups
Spotted fever groupRocky Mountain Spotted Fever
Other spotted fevers
Rickettsialpox
Typhus group
Epidemic typhus, Brill-Zinsser
Murine, scrub typhus
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Rickettsial properties
Coccobacillary, < 1 micron
Gram stain poorly, needGimenez
Have metabolic apparatus
Use host ATP, NAD, CoA Extracellular survival poor,
need vectors
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Rickettsial biology
Bacteria, not viruses
Clinical grouping Small, poor on Gram
Have metabolic paths
Perish outside cells
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Rickettsiae & spirochetes
Rocky Mountain Spotted
Fever
Rickettsial biology
Other rickettsioses
Spirochetes
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Other rickettsioses
Characteristics of a
typical rickettsial disease Diseases other than
Rocky Mountain Spotted
Fever
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Rickettsial epidemiology
Tick vectors (exceptions: typhus,
rickettsialpox)
Humans dead-end hostss
(exception: epidemic typhus)
Mid-spring/mid-summer peak
Vector digestive tract
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Typical rickettsial illness Inoculation eschar
(exception: Rocky MountainSpotted Fever)
Rickettsemia Endothelial growth
Vasculitis 1-2 week incubation Rash, fever, headache
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Rickettsial diagnosis
Must suspect clinically Immunoflorescent stained skin
biopsy Weil-Felix pass Serology usually (but delay in
getting results) Isolation hazardous Rule out others
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Rickettsial control
Public health
Reporting
Vector/reservoir
No vaccines
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Rickettsial diseases other than
Rocky Mountain Spotted Fever
Other spotted fevers (inother parts of world) Rickettsialpox (urban, from
mice and mites) Typhus group (epidemic
typhus from lice)
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Other rickettsioses
Vector (often tick)
Eschar, rickettsemia Vasculitis, serologic test
Includes spotted fevers,rickettsialpox, typhusgroup
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Rickettsiae & spirochetes
Rocky Mountain Spotted
Fever
Rickettsial biology
Other rickettsioses
Spirochetes
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Vincents infection/Trench mouth
Necrotizing ulcerative gingivitis
Synergistic gum infection
Occurs in poor oral
hygiene, malnutrition,
immunocompromise
Penicillin, oral hygiene
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Relapsing Fever
Epidemic Endemic
B. recurrentis Lice
Human-lice
E. Africa,
Andes
Borrelia spp Ornithodoros tick
Human intruder
Worldwide: High,
warm, humid
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Relapsing fever
pathogenesis Spirochetemia
Sequestration Antigenic modification
Widespread (liver, spleen,CNS, heart, GI, kidney)
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Relapsing fever presentation
Abrupt fever, malaise,
headache
Arthralgia, cough, photophobia
Conjunctival suffusion
Petechiae
Abdominal tenderness
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Relapsing fever
Recovery in 3-6 days
Relapse in 7-10 days
Untreated, 40% die
Blood smear positive 70%
Tetracycline,chloramphenicol
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Lyme disease, United States
L di b t US 1999
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Lyme disease by county, US, 1999
0
00 1-14 > 15 cases
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North Central Northeast
Lyme disease, by county, 1996
5-9 10-29 >30
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Lyme disease cases
by month, US, 1999
0
1000
2000
3000
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
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Erythema chronicum
migrans
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Early Late
Da-wk Da-mo Mo-yr
ECM Nerve JointJoint Fatigue
Heart
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Lyme diagnosis and
treatment Clinical, with special serology
Treatment depends on stage
Doxycycline, amoxicillin,cefuroxime
IV penicillin or ceftriaxone(later)
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Tick repellent
DEET
Skin, clothingCNS toxicity (directions)
Permethrin: Clothing
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Doxycycline vs. placebo after tick bite,
N Engl J Med2001EM OK
Doxy 1 234
Placebo 8 239
Event OK
47 109
17 136
No one developed extra-cutaneous Lyme disease.
Advice: Treat in high-risk areas.
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Key points: Lyme disease
Tickborne B. burgdorferi
Local: Erythema migrans Dissem: Heart, nerve, joint
Persist: Fatigue, joint Doxycycline, ceftriaxone
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Frontiers of prevention
Vaccine: Withdrawn
Tick avoidance
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Many spirochetes tickborne
Not tickborne
Syphilis: Sex
Leptospirosis: Animal urine;early conjunctival suffusion,later liver & kidneys
Tickborne: Borrelia relapsingfever, change antigens & relapse
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Spirochetal disease parallels
Lyme (& Syphilis)
Initial rash: Erythema chron. mig.
2 stage: Nerves, heart, joints
Late stage: Arthritis, fatigue
Treatment: Penicillin, tetracycline
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Rickettsia and spirochetes
Rocky Mountain SpottedFever
Headache, rash, fever
Tickborne
No growth on routineculture
Doxycycline
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Rickettsia and spirochetes
Other rickettsia
Poor extracellularsurvival
Suspect clinicallyTyphus: humans, lice
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Spirochetes
Sequestration, antigenic
change in relapsing fever Erythema chronicum
migrans, tick in Lyme