Unit 2 - Vector-Borne Spirochetes and Rickettsia Flashcards

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1
Q

what is the bacteriology of Borrelia burgdorferi?

-shape? stains?

A
  1. motile spirochete - flat-wave shape

2. stainable with giemsa, silver stain, IF; visible by standard microscopy

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2
Q

epidemiology of B. burgdorferi? vectors? how long does it take to transmit?

A
  1. tick-borne (I. scapularis in east, I. pacificus in west), most common one in US, esp east (when deer herds increase)
  2. highest risk in summer (many nymphs are feeding on many people)
  3. small mammal reservoirs (rodents) preferred by nymphs; large hosts (deer) by adults
  4. almost always requires 24 hours attachment to transmit
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3
Q

how does one remove ticks with Lyme? treatment?

A
  1. tweezers + gloves
  2. bag + freeze (can culture B. burgdorferi from tick, seldom positive from humans)
  3. promptly (needs 24 hours to transmit)
  4. doxycycline if the patient is not pregnant or allergic to tetracyclines
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4
Q

explain the pathogenesis of Lyme disease?

A

asymptomatic clearance possible

  1. symptoms spread from bite site to blood (bacteremia) to hearts, joints, CNS
  2. doesn’t involve toxins, as is primarily immune evasion
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5
Q

what is the timeline for Lyme disease?

A

6 mo after bite, organism spreads

  • erythema migrans rash (75%), anti-spirochete Ab raised
  • very persistent skin infection established

months to 1 year after infection, immune and/or neurological issues arise
-arthritis predisposed by HLA-DR4/2 genotymes, and by certain strains of B. b.

post-Lyme, 80% of untreated/undertreated cases report nerological sequelae
-reinfections occur

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6
Q

what is the diagnostic exam for Lyme disease?

A

get history of outdoor activity (season and location)

  • divided into 4 stages:
  • -1 (days) erythema chronicum migrans
  • -2 (months) cardiac and neurological involvement
  • -3 (months) arthritis in large joints
  • -4 (post-treatment) fatigue, joint pain, mental status changes
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7
Q

what is the rash when a tick is still attached? what must you be aware of?

A

hypersensitivity, not Lyme (yet)

-coinfection with Ehrlichia or babesioa (b/c all tick-borne) will cause high fever

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8
Q

what is stage 1 Lyme?

A

(days) : erythema migrans expanding rashes at/near bite site (bull’s-eye minority)
- may have flulike symptoms (fatigue, aches, lympadenopathy, fever)

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9
Q

what is stage 2 Lyme?

A

(months) : musculoskeletal and/or neurologic symptoms
- intermittent arthritis lasting about a week, and recur (esp. knee)
- aseptic meningitis, Bell’s palsy, particularly bilateral facial nerve palsy (MRI/CT useful)
- rarely cardiac involvement (arrhythmia or transient block, EKG; must admit)
- rarely ophthalmic symptoms

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10
Q

what are unique features of Lyme disease in Europe?

A

occur in stage 2 (months)

  • bluish borrelial lymphocytoma on earlobe (peds) or nipple (adult)
  • chronica atrophicans: progressive fibrosing skin process on extremities
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11
Q

what is stage 3 Lyme?

A

months: now chronic Lyme disease
- arthritis in large joints (knees)
- subacute encephalopathy
- chronic progressive encephalomyelitis
- late axonal neuropathies
- fibromyalgia
- patients may recall earlier episodes of Bell’s palsy, aseptic meningitis

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12
Q

what happens in post-treatment Lyme?

A

lingering fatigue, joint pain, mental status changes

-never back to 100%`

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13
Q

what happens in Lyme lab?

A
  1. serology, ELISA, and IFA can confirm exposure, but not current activity, and not until 6-8 weeks later
    - patients with the vaccine will be seropositive, and seropositivity remains long term
    - equivocal-positive titers can be confirmed by Western blot or PCR
    - seronegativity is reliable (consider alternative diagnoses)
    - elevated synovial and spinal fluid cell coints suggest current activity
    - biopsy of lymphocytoma or acrodermatitis may be useful
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14
Q

are Ab raised against Lyme protective?

A

no, they are not protective

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15
Q

what should one lab for Lyme if one has neurological symptoms?

A

CSF should be examined for mononuclear cells and anti-Lyme IgM, IgG
-remember that Ag = exposure, NOT current disease

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16
Q

treatment for Lyme? what should you do if the erythema migrans expands?

A
  • if stage 1 (mild): doxycycline or amoxicillin
  • improves rapidly with antibiotics, but only for 2 months (contraindicated if pregnant/peds)
  • if late stage (severe): ceftriaxone
  • will see Jarisch-Herxheimer reaction
  • rash may expand for 2-3 days, but DON’T add steroids for arthritis
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17
Q

prevention of Lyme?

A
  1. protective clothing, DEET, avoiding woods, tick collars on pets
  2. daily close inspection for family and pets
  3. prophylaxis with doxycycline may be recommended in some geographic areas, and if tick attached >24 hr
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18
Q

what is the bacteriology of relapsing fever? pathogens? vector? reservoir? endemic? transmission?

A

includes both Borrelia recurrentis and hermsii
-both microscopically visible on blood smears and grow on special media

B.r. vector is body louse, reservoir is human

  • endemic to Africa and homeless shelters
  • transmit by louse crushing/inoculation by scratching (b/c louse feces/blood gets into bloodstream)

B.h. et al fector is soft ticks, reservoir is small mammals and ticks

  • endemic to W. US, S. BC, Mexico, C/S. America, Asia, Africa, Mediterranean
  • transmit by bite (usually nocturnal, unnoticed)
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19
Q

pathogenesis of relapsing fever?

A
  1. spirochetes invade blood from bite site, access vasculature, and multiply in many tissues (spleen, BM, liver, lungs, kidneys, CNS)
  2. general malaise and organ dysfunction follow
  3. neutralizing Ab and strong IL-10 response develop and halt sepsis –> fever
  4. selective pressure for Ag variation; bacterial surface Ag not recognized by current Ab come to predominate
  5. disease resumes, and cycle repeats (as immune response improves, lower fever and longer breaks)
    - pathogenesis doesn’t seem to involve toxins, primarily immune evasion
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20
Q

what is the average relapse and mortality of louse-borne relapsing fever?

A

(B.r.)
average of 1 relapse
-mortality 4% if treated, 40% if untreated

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21
Q

what is the average relapse and mortality of tick-borne relapsing fever? complications?

A

(B.h.)
average of 3 relapses
-mortality <2% if treated, 4-10% if untreated
-causes complications in pregnancy (abortion, premature birth, neonatal death up to 50%)

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22
Q

what does the exam look like for relapsing fever?

A
  1. history (2+ episodes of 3-5 days of high fever >39C with low BP, then well week between)
  2. chills, arthralgias, N/V, ab pain, mental changes, nonproductive cough, dizziness, diarrhea,, neck pain, photophobia, rash, dysuria
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23
Q

what are louse-specific exam findings for relapsing fever?

A

B.r. causes jaundice, petechiae, hemoptysis, epistaxis, and CNS involvement

24
Q

what are lab findings in relapsing fever?

A
  1. peripheral blood smear: spirochetes visible by microscopy with Wright or Giemsa stain if blood taken during febrile period
  2. can visualize bacteria with IF, darkfield, wet mounts, silver-stained biopsies
  3. CSF: mononuclear pleocytosis
  4. organism can be cultered from blood in special liquid medium, takes 2-6 weeks
  5. PCR assay and ELISA available
25
Q

treatment of relapsing fever? doses for louse VS tick-borne?

A
  1. tetracycline, doxycycline, erythromycin, penicillin G in adults
    - takes 1 dose if louse-borne B.r., 7-10 days for tick-borne B.h.
  2. erythromycin in children and pregnant/nursing women
  3. IV penicillin or ceftriaxone for meningitis
  4. Jarisch-Herxheimer reaction
26
Q

prevention of relapsing fever?

A
  1. prophylaxis with doxycycline may be recommended after expore
  2. tick-borne: avoid rodents, use protective clothing, DEET
  3. louse-borne: delousing (social policy, hygeine, 1% lindane, DDT powder, Lysol)
27
Q

how are Rickettsia lke and unlike Borrelia?

A

similar: Arthropod vectors, mammalian reservoirs, and tetracycline sensitivity
different: small cocci to short rods (Borrelia are spirochetes), intracellular replication

28
Q

what are the Rickettsial pathogens? what diseases do they cause?

A
  1. Rickettsia: spotted fever and typhus (NOT typhoid fever)
  2. Coxiella burnetti: causes Q fever (not actually related to any of other three)
  3. Ehrlichia: human and canine monocytic ehrlichiosis
  4. Anaplasma: human granulocytic ehrlichiosis and anaplasmosis
29
Q

bacteriology of Rickettsia?

A

very short rods, hard to G stain (-)

  • all use arthropod vectors (except Q fever’s Coxiella)
  • obligate intracellular parasites (binary fission in tissue culture, eggs, or animals)
  • easily enter bloodstream –> bacteremia
30
Q

when do most Rickettsia infect humans?

A

by accident

31
Q

pathogenesis of Rocky Mountain Spotted Fever?

A

Rickettsia vectored by ticks

  • bacteremia
  • invade and multiply in vascular endothelium
  • blood vessels leak as infected cells die –> rash
32
Q

virulence factors of Rocky Mountain Spotted Fever? what they do?

A
  1. Omp A+B: adhesion
  2. Type 4 secretion system: entry
  3. Phospholipase A2: escape from endosome
  4. ActA: actin-based cell-cell spread
33
Q

presentation of RMSF?

A

most dangerous to previously healthy patients

  1. begins nonspecific: headache, fever, myalgia
    - vasculitis –> rash begins on extremities, spreads to trunk (common, but not universal)
  2. may progress to delerium, coma, DIC, edema, circulatory collapse (18% untreated mortality)
    - most common on East Coast (dog tick), which may not be recalled
34
Q

treatment for RMSF?

A

prompt and appropriate antibiotic treatment is critical

  • doxycycline works so well that treatment failure suggest misdiagnosis, but unsafe in pregnancy
  • -allowed in children
  • chloramphenicol is alternate for pregnant/allergic patients
35
Q

risk factors for poor RMSF prognosis?

A
  • age > 40 yrs

- antibiotic treatment delayed/absent

36
Q

prevention of RMSF?

A

protective clothing, insect repellent

37
Q

pathogenesis for Mediterranean spotted fever?

A

less common member of spotted fever group, less severe
-transmitted by dog tick in Europe, Africa, Central Asia (not US)
-begins with eschar (black cigarette spot) at site of tick bite
severe cases arise if predisposed (older age, alcoholism, G6PD deficiency)
-same treatment as RMSF (doxycycline)

38
Q

explain epidemic typhus?

A

Rickettsia prowazekii

  • unlike other Rickettsia, humans are normal host and reservoir
  • vectored by body louse, sometimes head/pubic lice
  • organism comes from previous human’s blood (rickettsemia) which multiplies in louse GIT
  • louse eventually dies of infection (obstruction; spreads by poop’n’scratch)
  • bacteria multiply in vascular endothelium (same Omp A/B surface adherence as RMSF) –> vaculitis
39
Q

symptoms of epidemic typhus?

A
  1. abrupt onset fever, chills, unremitting headache
    - generalized lymphadenopathy
  2. macular, maculopapular, or petechial rash occurs on days 4-7
    - may start on axilla and trunk, and spread peripherally (RMSF rash begins on extremities and spreads centrally)
  3. CNS symptoms may include dullness, delerium, coma
    - less common is nonproductive cough, deafness
  4. untreated course 2 weeks, mortality from vascular collapse or pneumonia (20-60% untreated)
    - several months may pass before complete recovery
40
Q

what is important to gain from typhus patient history?

A
  1. louse bite
  2. natural disaster or war
  3. medical/military personnel
  4. overcrowding
  5. lack of personal hygiene
  6. season (cold = epidemic typhus, warm = murine/scrup typhus)
41
Q

what is Brill-Zinsser disease?

A

recrudescent epidemic typhus (reemerging)

  • mechanisms of latency and reactivation are unknown
  • less severe than initial course
  • risk factors include malnutrition and improper/incomplete antibiotic therapy
  • may be seen in US among geriatric patients who had typhus during WWII
42
Q

how is epidemic typhus unlike spotted fevers?

A
  • humans are proper host of bacteria
  • lice, and not ticks, are vector
  • disease often returns in recrudescent form
43
Q

what is murine typhus?

A

flea-borne endemic typhus (Rickettsia typhi)

  • milder than epidemic typhus
  • accidental transmission to humans of cat/rat typhus
  • southern and southwest US
  • more common in warm weather
44
Q

what is scrub typhus?

A

humans are accidental host to Leptotrombidium akamushi (chigger) and O. tsutsugamushi bacterium

  • milder than epidemic typhus, more common in warm weather
  • 60% form Eschar at bite site
  • regional lymph node and pulmonary involvement (cough) more common
45
Q

treatment of all types of typhus

A

begin antibiotics before final confirmation (from immunofluorescence assay or enzyme immunoassay)

  • use doxycycline or chloramphenicol
  • if recrudescent disease, second course of antibiotic enough
  • azithromycin and rifampicin are effective if known doxycycline resistance
46
Q

prevention of typhus?

A

epidemic: hygiene and delousing

murine/scrub: protective clothing, insect repellent

47
Q

Ehrlichia chaffeensis bacteriology?

A

causes human monocytic ehrlichiosis

  • tiny G- rod that is obligate intracellular parasite
  • resembles Rickettsia
  • replicates in cytoplasm of white cells
  • forms clusters (morulae)
  • vectored by ticks among reservoirs (small/large mammals) and accidentally transmitted to humans
48
Q

pathogenesis of human monocytic ehrlichiosis

A

often asymptomatic, but can proceed to flulike symptoms, GI symptoms (within a week); meningitis, and/or DIC (if elderly or immunocompromised)
-may coinfect with another pathogen by same factor (must rule out babesiosis and Lyme)

49
Q

how to diagnose human monocytic ehrlichiosis?

A
  1. patient history: travel to endemic areas, hiking
  2. CBC (neutropenia, lymphocytopenia, thrombocytopenia)
  3. serum transaminases (often tickborn)
  4. morulae
  5. confirm by PCR or immunostaining
50
Q

treatment of human monocytic ehrlichiosis?

A

begin antibiotics without delay (doxycycline unless pregnant)
-chloroamphenicol is not effective, but fluoroquinolones may be

51
Q

what are human granulocytic ehrlichiosis/anaplasmosis?

A

diseases caused by Anaplasma

-clusters of small bacteria noted within neutrophils

52
Q

bacteriology of anaplasma

A

small, G- obligate intracellular

  • survive and multiply in early endosome of WBC
  • grow into morulae
  • vectored by ticks, reservoir is small/large mammals
53
Q

what are the only known organsism to grow within neutrophils?

A

Ehrlichia, anaplasma, and C. pneumoniae

54
Q

diagnosis of human granulocytic anaplasmosis?

A

present: fever, headaches, myalgia, malaise, absence of skin rash
history: travel to endemic areas, hiking
CBC: neutropenia, lymphocytopenia, or thrombocytopenia
-serum transaminases and morulae
-confirmed by PCR or immunostaining
-rule out babesiosis and lyme
-5-7% of cases require intensive care

VERY SIMILAR TO HUMAN MONOCYTIC EHRLICHIOSIS

55
Q

human granulocytic anaplasmosis treatment

A

begin antibiotics without delay (doxycycline unless pregnant)
-chloroamphenicol is not effective, but fluoroquinolones may be

IDENTICAL TO HUMAN MONOCYTIC EHRLICHIOSIS