2: Rickettsial + Zoonotic Flashcards
vector borne diseases: intracellular vs. extracellular + vectors
intracellular:
- rickettsial typhus (lice)
- rickettsial RMSF (ticks)
extracellular:
- lyme disease (ticks)
- relapsing fever (lice or ticks)
- plaque (fleas)
histologic hallmark of rickettsia
‘perivascular cuffing’ - intracellular infection of endothelial cells w/ perivascular lymphocytic infiltrate
general characteristics of rickettsia
G(-)
obligate intracellular
rickettsia transmission
by arthropod (ticks, mites, fleas, lice) bite or contamination of abraded skin with arthropod feces
what might a patient have at the inoculation site for rickettsia?
eschar - dark, swollen, crusted, necrotic lesion
how is rickettsia diagnosed?
- immunostaining of organisms
- anti-rickettsial serology
- exposure to vector
(not by culture - will not grow)
pathogenesis of rickettsia and what it causes
multiply mainly in small vessel endothelia - causes secondary vascular leakage:
- rash
- fever
- CNS manifestations
- small vessel vasculitis w/ microthrombi, focal ischemia, or hemorrhage
- lyse endothelial cells (typhus) or spread cell to cell (spotted fever group)
- may progress to hypovolemic shock w/ peripheral edema
perivascular cuffing
MAKE SURE TO STUDY PICTURES IN THE PACKETS TOO
what is responsible for much of the tissue damage seen in rickettsial disease?
NK cells produce gamma-IFN -> cytotoxic T cell response responsible for damage
clinical features of rickettsia
- fever
- rash
- CNS symptoms
severe cases:
- hypovolemic shock
- DIC
- pulmonary edema
- gangrene
- petechiae
which clinical feature of rickettsia is also seen in N. meningitidis G(-) sepsis and how do you differentiate the two?
sx of sepsis/shock - differentiate based on context
what other diseases are on the ddx for rickettsia?
-meningococcemia
-rubeola
-rubella
-ehrlichiosis
(last three are way down on the list b/c they almost never cause shock and DIC)
transmission of epidemic typhus and what organism causes it
caused by Rickettsia prowazekii
head lice mediates human to human transfer
forms of disease for epidemic typhus
- begins with centrifugal rash
- followed by CNS shit (apathy, dullness, stupor, some coma)
- high fever
- chills
- cough
- rash
- severe muscle pain
- sensitivity to light
- delirium
if epidemic typhus is untreated, what is the mortality rate?
10-60%
clinical findings of mild epidemic typhus
- rash
- small hemorrhages
clinical findings of severe epidemic typhus
-gangrene of finger tips, nose, earlobes, scrotum, penis, vulva
histologic/morphologic findings with epidemic typhus
- cuff of mononuclear inflam cells around vessels
- ecchymotic hemorrhages of affected organs
- microthrombi
- no necrosis of vessels
transmission of RMSF
dog or wood tick bite
incubation period of RMSF
7d
symptoms of RMSF
- high fever for 2-3d
- nausea
- vomit
- headache
- muscle pain
- rash appears 6d of fever (b/c lymphocytes now attacking vessels - microthrombi add to rash)
- hemorrhagic rash extends over entire body (including PALMS AND SOLES)- spreads periphery to trunk/neck/face
- eschar rare
histologic/morphologic findings with RMSF
- perivascular mononuclear infiltrate
- necrosis, fibrin extravasation, and thrombosis of small vessels and arterioles
- severe: foci of necrotic skin (fingers, toes, elbows, earlobes, scrotum)
- microinfarcts in brain
- noncardiogenic pulmonary edema
what is the major cause of death in RMSF
noncardiogenic pulmonary edema
how to differentiate noncardiogenic pulmonary edema from cardiogenic pulmonary edema
non: lymphocytes in this fluid, it is an exudate
cardio: transudate! and no lymphocytes
area distribution of RMSF by tick
dog tick: east
wood tick: west
if you get these symptoms in winter vs. summer, what is more likely: RMSF or meningitis?
winter: meningitis
summer: RMSF
what causes scrub typhus and where do you find it?
Orientia (formerly Rickettsia) tsutsugamushi
endemic in Far East, China, India
how is scrub typhus different from epidemic typhus?
- resembles typhus but transmitted by mites
- transitory or no rash
- may be prominent lymphadenopathy
compare/contrast ehrlichiosis and RMSF
similar, but ehrlichiosis has:
- no eschar
- rash rare (b/c infects neutrophils/monocytes instead of endothelial cells)
- characteristic cytoplasmic inclusions (morulae)
- transmission by ticks
describe the morulae of ehrlichiosis
masses of bacteria that look like mulberries in shape
transmission of lyme disease (borrelia burgdorferi)
spirochetes transmitted to man by tick bites from animals or lice (man to man)
-white-tailed deer tick
how is borrelia burgdorferi able to persist in the body?
shift antigenic markers to avoid host production of Ab’s
-get local rxn when organism first injected, but then can persist and spread - chronic problems + can cause tertiary problems down the road (CNS, heart, joint)
area distribution of lyme disease
wisconsin/minnesota + northeast coast US
-near boundary waters
what two bugs should you think of when someone has recently traveled by boundary waters?
giardia and lyme disease
describe lyme disease multisystem chronic inflammatory disorder
local lesion progresses to bacteremia and chronic inflammatory lesions in distant organs
-primary/secondary/tertiary disease
what is much of the pathology thought to be due to in lyme disease?
secondary to immune response against bug:
-binding of bacteria LPS to TLR2** of macrophages
lyme disease prevention?
OspA vaccine commercially available for high risk groups
vector avoidance
treatment for lyme disease
doxycycline
describe primary lyme disease
- skin rash (target lesion/Bull’s eye rash) w/ vasodilation and dense perivascular inflammatory infiltrates of mononuclear leukocytes
- rash has spreading erythematous margins and blanching center (erythema chronicum migrans)
- fever and constitutional symptoms
- resembles rickettsial illnesses such as RMSF
describe secondary lyme disease
- months later
- bacteremic dissemination fo spirochetes
- joint disease
- muscle pain
- cardiac arrhythmias
- meningitis
- CN involvement
describe tertiary lyme disease
- years later
- CNS
- cardiac
- skeletal
describe progression of lyme disease from primary to secondary to tertiary in general terms
local primary rxn -> disseminated rash -> tertiary localized, chronic rash
pathology of lyme disease
- focal necrosis, hemorrhages, DIC
- skin rash w/ dense perivasular mononuclear infiltrate
- lymphoplasmacytic cell infiltrate!!! (only syph and lyme)
describe arthritis of lyme disease
resembles early rheumatoid arthritis:
- synovial hyperplasia
- lymphocytes, plasma cells
- proliferative arteritis
transmission of relapsing fever (borrelia recurrentis) and area distribution
- spirochete transmitted by human lice or rodent ticks to humans
- throughout world
- epidemics in Africa, E Europe, Russia
latent period of relapsing fever
1-2w of shaking chills, fever, headache, fatigue
what causes the successive attacks (epochs) of relapsing fever?
- ability of the dude to express new surface Ag’s
- with each wave of attack, body must make new Ab’s
what is fatal relapsing fever accompanied by?
massive hepatosplenomegaly
organism and transmission of plague
- yersinia pestis
- arthropod bite (fleas!)
- man an accidental victim of ‘sylvatic cycle’ b/w fleas and wild animals
pathologic mechanisms of plague
- rapid proliferation within lymphoid tissues**
- “injection” of YOPS (yersinia outer proteins)
- necrosis of tissue and blood vessels
- swelling of lymphoid tissues (buboes)
- striking leukocytosis
- septicemia/DIC -> Death
describe the function of YOPS in plague
- inactivates molecules that regulate actin polymerization
- inhibits secretion of inflammatory cytokines
symptoms of minor plague
- lymphadenopathy
- constitutional symptoms
symptoms of bubonic plague
-prominent lymphadenopathy (buboes)
symptoms of pneumonic plague
-hemorrhagic, necrotizing pneumonia primary or secondary to bubonic infections
most common form of plague?
bubonic plague
can you get sepsis from plague?
yes, and it is rapidly fatal
but rare in US
mortality of plague untreated and treated + what is treatment
untreated: 50-90%
treated: 15%
doxycycline for the win!
what is the primary immune response to intracellular dudes?
cytotoxic T cells
what symptoms will you get from all disease that cause microthrombi in the brain?
- obtundation
- headache
- seizures
besides Rickettsia, what other diseases also cause microthrombi in CNS?
- malaria
- TTP
- eclampsia
flowchart of rickettsial pathogenesis
intracellular dude gets in-> endothelium activated + perivascular lymphocytes -> microthrombi + microhemorrhages
