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28 Spirochetes Rickettsia

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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


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