FM3 Part 2 Flashcards
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
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
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
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)
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
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
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
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
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)
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]
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)
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
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
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
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%)
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
Identify the limitations of the Gram stain for rickettsia.
rickettsia: fastidious, obligate intracellular pathogens
- coccibacillary bacteria (appear pleomorphic) => use Giemsa stain (≠ Gram stain)
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)
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)
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
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)
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
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
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
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
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
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
