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Flashcards in FM3 Part 2 Deck (27):
1

Lyme Disease: cause

vector: tick
- carries Borrelia burgdorferi: spirochete in small animals (mice, squirrel) => NOT deer
o array of outer-surface proteins (Osp A-F) to adapt to host
o virulence: lipoproteins (surface), no toxins

- NE + N. Central US: black-legged tick (deer tick, Ixodes scapularis)
- Pacific US: Pacific black-legged tick (Ixodes pacificus => also carry anaplasmosis

2

Lyme Disease: epidemiology

most common vector-borne illness in U.S. + Europe
- found in all 50 states (esp. New England, upper Midwest, mid-Atlantic)
o white-footed mouse + white-tailed deer = endemic
- bimodal distribution: 5-14 yo + 55-70 yo

3

Lyme Disease: risk factors

outdoor activities (camping, clearing brush, hunting, fishing, etc.)

risk of infection
- tick density
- tick feeding habits
- proportion infected w/B. burgdorferi
- animal host availability
- amt time outdoors

4

Explain how infection with B. burgdorferi is acquired (including the forms of tick that are infectious).

larva, nymph [most likely in human transmission], adult
o each requires a blood meal; 2 year cycle
o 10-50% nymph + adult ticks infected w/B. burgdorferi

adult: lay eggs in spring, hatch in summer (larva)

larva: feed on small animals (infected for life)

o B. burgdorferi in tick’s midgut

nymphs: need blood --> adults (transmit B. burgdorferi)

5

Lyme disease: pathogenesis

tick (nymph) climbs on lower leg (grass or shrubs)
- after 24 hrs = feeds [mouth parts inserted into skin, salvia = anti-coagulant/inflam.)
o human blood in midgut = B. burgdorferi out of salivary glands
• blood = increase water, excretes by injecting saliva
min. attachment time > 24 hrs (36-72 hrs range more typical)
incubation time: 7-14 days (up to 1 month)
o local multiplication (site of infection) => dissemination (blood, CSF, ♥, bone, muscle, retina)
o B. burgdorferi survives for yrs in skin, joints, CNS

6

Lyme disease: clinical presentation

stage 1: early localized infection: 7-14 day incubation (3-30 possible)
- most ≠ recall specific tick bite
erythema migrans (EM) at site of bite (70-80%) => thigh, butt, groin, axilla
o erythematous, homogenous, annular lesion [“bull’s eye” appearance]
o possible central necrosis or ecchymosis
fever, chills, malaise, arthralgia, myalgia, headache (increases with babesiosis co-infection)

stage 2: early disseminated infection: several wks after EM
- multiple (2°) EM lesions [organisms in skin]
MSK (60%): migratory joint, tendon, bursae, muscle pain
CNS (15%): meningitis, facial nerve palsy, radicular neuropathy (wks-months, recurrent/chronic)
CV (8%): AV block
ocular: EOM (ptosis, swelling) or C.N. involvement

stage 3: late disseminated infection: months after bite (60% un-TX)
- intermittent attacks of large joint arthritis (wks-months, chronic)
- encephalopathy: cognitive disturbances, insomnia, personality Δ
- polyradiculopathy: radiate from spine, paresthesias; spastic paresis, ataxia
- fatigue

7

Lyme disease: prevention

prevention: avoid tick bites (protective clothing + DEET)
remove ticks => monitor for signs/symptoms for 30 days
vaccine not on market (decreased effectiveness + arthritis??)

antibiotic prophy? not routinely recommended:
- single dose of doxycycline for adults/children >8 yo:
o attached tick/nymph for >36 hrs
o started w/in 72 hrs of removal
o local tick infection rate >20%
o no contraindications to doxycycline

8

Lyme disease: diagnosis

clinical DX (features in endemic area)
- most ≠ recall tick bite (black-legged ticks very tiny)
- labs unremarkable, PCR (+) on synovial fluid + skin biopsies
serology supportive: absent early, (+) IgG after 1 month, persist for yrs (≠ protection)
o even IgM (+) for years
o 2-step approach: ELISA + Western blot

Important:
1) DX clinically (presentation, setting, rx serologic test)
2) early localized Lyme = clinical DX [TX w/antibiotics, ≠ rely on serology]
3) serology ≠ distinguish past from active infection

9

Lyme disease: treatment

Doxycycline DOC [oral, effective, well-tolerated, TXs HGA]
o contraindicated: pregnancy, lactation, children use amoxicillin or cefuroxime

CNS, AV block, or persistent arthritis manifestations: ceftriaxone
o alternative = penicillin G
o Jarisch-Herxheimer rxn ~15% w/in first 24 hrs of TX

Arthritis w/o CNS: doxycycline, amoxicillin, cefuroxine axetil (28 days)

10

Lyme disease: specific complications

Lyme meningitis: aseptic profile (~100 cell/mL, N glucose, increased protein)
- headache, neck pain/stiffness, irritability
- Lyme Ig in CSF => TX w/ceftriaxone

Lyme carditis: lightheadedness, fatigue, AV block fluctuation, myocarditis possible
- few days to 6 wks => temp. pacemaker

Lyme arthritis: large joints (knee), synovial fluid = 500-100k cells/mL (PMNs)
- (+) PCR for B. burgdorferi
- most responsive to antibiotics, ~10% persistent (autoimmune??)

Post-Lyme disease syndrome (chronic Lyme disease): no DX criteria exists
- unexplained symptoms (fatigue, myalagias, arthralgias w/o arthritis, cognition/memory)
o > 6 months after antibiotic TX [no benefit from prolonged use]

11

Identify and categorize the bacteria that cause ehrlichiosis/anaplasmosis and how they are spread.

Anaplasma phagocytophilum (in granulocytes)

Ehrlichia chaffeensis (in monocytes)

Both: small GN obligate intracellular bacteria (leukocytes)

12

Name the two most common forms of ehrlichiosis/anaplasmosis and what category of blood cells each infects.

Human granulocytic anaplasmosis (HGA): Anaplasma phagocytophilum (in granulocytes)
- distribution + risks ~ Lyme b/c shares tick vectors (Ixodes scapularis, Ixodes pacificus)
o intercellular vacuoles = morulae (20-80%)
- reservoir: white-tailed deer

Human monocytotropic ehrlichiosis (HME): Ehrlichia chaffeensis (in monocytes)
- distribution ~ S. Central + SE U.S. b/c tick vector (Amblyomma americanum, Lone Star tick)
- reservoir: white-tailed deer

13

Describe the pathogenesis of ehrlichiosis/anaplasmosis.

24-48 hrs after tick bite = disseminate to bone marrow + liver/spleen
- infect granulocytes (HGA) or monocytes (HME), replicate
o find non-caseating, ~necrotizing granulomas in bone marrow + liver/spleen
o host inflammatory response = end organ pathology

incubation period: 7-10 days

14

Recognize the constellation of signs and symptoms suggestive of ehrlichiosis/anaplasmosis.

o mild to life-threatening: fever, headache, myalgias, malaise (~all)
• GI (NVD), arthralgias, cough, confusion (less than 50%)
• rash (10-40%): maculopapular more than petechial (more w/HME)

severe: septic shock, rhabdomyolysis, ARDs, renal failure, hemorrhage, CNS (meningoenc.)

Decreased CNS + mortality in HGA

immunocompromised: severe infection w/ increased mortality

15

Discuss how a diagnosis of ehrlichiosis/anaplasmosis can be made

clinical DX (acute phase) => TX ASAP (don't wait for diagnostic tests to come back; the rapid response to antibiotics will help to confirm diagnosis before PCR)
o peripheral blood smear for morulae (PMNs 20-80%, monos rare)
o PCR (widely used, takes awhile), serology response

Labs:
-low platelets (by days 1-3)
-low WBC/lymphopenia (by day 3)
-anemia (slow decline over days 7-14)
-High ALT and AST (by day 1)
-High creatinine (24-70%)

16

Discuss the general form of therapy of ehrlichiosis/ anaplasmosis (including class of antibiotics to be used).

Doxycycline for 10-14 days (start ASAP!!)
• improvement w/in 24-48 hrs (confirm DX), hematologic 2-5 days, ALT/AST 2-3 wks
o un-TX: 2-3 wks, up to 2 months

17

Identify the limitations of the Gram stain for rickettsia.

rickettsia: fastidious, obligate intracellular pathogens
- coccibacillary bacteria (appear pleomorphic) => use Giemsa stain (≠ Gram stain)

18

Examples of Rickettsia groups/types of diseases

Spotted fever group:
- Rocky Mountain spotted fever (Rickettsia rickettsii)
- Rickettsial pox
- Canadian typhus
- Mediterranean spotted fever
- African tick-bite fever
- Siberian tick typhus
- Queensland tick typhus

Typhus group:
- murine typhus (fleaborne typhus): Rickettsia mooseri [typhi]
- epidemic typhus = Brill-Zinsser disease = louseborne typhus: Rickettsia prowazekii

Q fever (Coxiella burnetii)

Endemic in U.S:
-Q fever (Coxiella burnetii)
-Murine typhus (fleaborne typhus): Rickettsia mooseri [typhi]
-Rocky Mountain spotted fever (Rickettsia rickettsii)

19

Describe how these obligate intracellular pathogens are transmitted to humans

Anthropod vectors: bite of insect (flea or louse) or arachnid (tick or mite) => eschar
- host + vector => reside on reservoirs (dogs, mice, rats, flying squirrels)

Inhalation: Q fever (Coxiella burnetii) + epidemic typhus (Rickettsia prowazekii)

20

Explain the pathogenesis of these organisms and link this with the clinical manifestations seen in rickettsial infections.

Same regardless of species!
Vasculitis: invasion + multiplication of organism in endothelium + smooth muscle cells
o causes thrombosis, occlusion, necrosis of endothelium

Thrombocytopenia from plt consumption (no “true” DIC)

Capillary leakage = edema + hypovolumia + decreased BP + ARDS!!
o hypovolumia --> ADH production --> hyponatremia
sequelae: encephalitis, myocarditis, nephritis

21

Rocky Mountain Spotted Fever

(Rickettsia rickettsii)
vector = tick
- spring or summer, Southeast U.S.(esp. North Carolina)
- incubation 2-14 days (7 median)

Classic triad: fever + severe headache + rash [+ travel HX]
- petechial rash: 3-5 days of illness, start at wrists + ankles --> trunk [centripetal rash]
o palms + soles = classic (~50-80%)
o ~10% = no rash [“spotless RMSF”]

other symptoms: myalgia, abdominal pain, NV => no eschar at tick bite site
o periorbital edema (+ hands/feet) + conjunctivae suffusion

DX: clinical, confirmed w/IFA (2-3 wks for results)

22

Epidemic Typhus

(Rickettsia prowazekii)

vector = human body louse
Lethal epidemics: war, natural disasters, great poverty => can’t bathe/wash clothes in hot water
o louse lives in clothes: blood meal multiple times/day
o infected w/biting rickettsemic person => sheds via fecal material
• scratching infects non-infected person w/R. prowazekii
• louse dies from rickettsial infection

incubation period 8-16 days: fever, severe headache, myalgias, central rash
o mental status Δs (stupor + coma)
o un-TX = 20-40% mortality
Southeast U.S. (flying squirrels = reservoir)
o Brill-Zinsser: mild, recrudescent form (mon-yr) after initial acute infection

23

Q Fever

(Coxiella brunetti) “poker player’s pneumonia”

vector = none (inhalation)
- inhale aerosolized organism (urine/feces/milk/placenta of sheep, cattle, goats)
- occupational disease: vets, farmers, ranchers, animal researchers
o indirect contact miles from 1° source => bioterrorism threat

incubation period 10-28 days (long)
o range: self-limited fever, Q fever pneumonia + severe headache, hepatitis, endocarditis
• atypical pneumonia (no organism w/sputum)

histology: donut-shaped, non-caseating granuloma

DX: serology
- un-TX = 25% mortality

24

Explain how rickettsial infections are diagnosed and treated

clinical DX: delay in serology (confirm) + epi risks + clinical manifestations

serologic DX: more specific + sensitive
- e.g. IFA, indirect hemagglutination antibody (IHA), complement fixation (CF)
- want 4x increase => several weeks

Weil-Felix rxn: historical lab test (insensitive + nonspecific agglutinin) => rarely done
- measures Ig that rx to Proteus OX:2, 19, or K antigens

TX: doxycycline, tetracycline, chloramphenicol => doxy preferred (even in children!!)
- prognosis based on timeliness [TX ASAP!]
o early antibiotic TX prevents severe vascular endothelial damage + organ failure

25

Explain how rickettsial infections can be prevented.

- min exposure to arthropods (repellents + protective clothing)
- inspect + remove tick
- ID + TX lice infestation
- vaccinate high-risk groups (e.g. forest rangers in NC)
- weekly doxycycline prevent scrub typhus in field workers

26

Identify the emerging concern about rickettsia related to returning international travelers

international travelers:
- most: murine typhus, scrub typhus, Mediterranean spotted fever, African tick-bite fever

27

Distinguish Mediterranean spotted fever from African tick-bite fever.

Mediterranean Spotted Fever (Rickettsia conorii)
vector = dog tick
- Europe (S. France + Spain), Africa, Asia + HX of contact w/local dogs
- fever, constitutional symptoms, generalized flat red rash, eschar
o most mild, some CNS or peripheral gangrene

African Tick-Bite Fever (Rickettsia africae)
vector = cow tick
- most common in travel: sub-Saharan Africa (esp. South Africa)
- cow ticks aggressive! + reside on vegetation (walk thru brush = safaris, walk outdoors)
- headache, myalgia, 1+ eschars, regional lymphadenopathy
o 30% = mouth blisters + disseminated vesicular rash
o self-limited, mild