Vector borne agents Flashcards
3 diseases caused by vector borne bacterial agents
- Lyme Disease
- Rocky Mountain Spotted Fever
- Plague
- arthropod vector
At least 3 closely related species can cause Lyme disease: Borrelia burgdorferi, Borrelia garinii, Borellia afzelii. Which is found in the US?
B. burgdorferi
What is the B. burgdorferi vector?
-black legged tick (Ixodes)
Why is simple removal of the Ixodes tick enough to prevent Lyme disease if it has already bitten you?
-takes 2-3 days for transmission of bacteria
Ticks have 2 year life cycles and what are the 4 stages?
- eggs hatch into larvae
- larvae develop into nymphs
- nymphs progress to adults
- female adults lay eggs
- blood meal between each stage of maturation*
Characteristic rash of Lyme Disease
-Erythema migrans: bull’s eye rash
Borrelia burgdorferi is what shape of bacterium?
-spirochete
Species of ticks and regions they infect with Lyme Disease
- Ixodes scapularis (deer tick) in NE and North central US
- Ixodes pacificus on pacific coast
Which phase of the tick life cycle is most likely to bite humans?
-nymph
In the East and Midwest, the most common animal reservoir for B. burgdorferi is…
- white footed mouse
- deer are also important but only because they are the principal host for adult tick
Why do most cases of Lyme Disease occur in the summer?
-nymphs feed during late spring and early summer and are the form of tick most likely to transmit bacteria to humans
I.neotomae is the main vector for Lyme Disease on the West coast. What is the reservoir and why does this not get to humans?
- woodrat
- I. neotomae doesnt bite humans
T/F: I. Pacificus prefers to eat lizards, which are not a reservoir for B. borgdorferi, but occasionally will feed on a woodrat and become infected and transmit to humans this way.
true
Why aren’t lizards susceptible to Borrelia infection?
-due to complement-mediated killing of the bacteria in lizard blood
What can explain the increase in Lyme Disease prevalence?
- increased exposure to agent
- increased awareness/diagnosis of the disease
Lyme Disease is a good example of an _______ disease.
-emerging
Who is at risk for Lyme Disease?
- people whose jobs involve landscaping, brush clearing, forestry, or park management in endemic areas
- work or play in yard or hike, camp, and hunt
- people living or work in residential areas surrounded by tick-infested woods or brush
Structure and physiology of B. burgdorferi
- spirochete, gram negative, extracellular
- helical, flexible cylinder with 7-11 periplasmic flagella and an outer membrane that is loosely associated with underlying structure
- highly motile
T/F: B. burgdorferi causes disease via toxins
-false; causes disease due to its ability to migrate through tissues, adhere to host cells, and evade host immune system
What is unique about B. burgdorferi’s genome?
- about 40% on plasmids
- huge proportion dedicated to lipoproteins which are located on bacterial surface
________ is the key step in Borrelia infection in both arthropod vector and mammalian host. What probably mediates this?
- Attachment
- outer surface proteins (Osps) A-F
Explain how tick feeding induced an adaptive response that facilitates spread of Borrelia from tick to host.
- OspA is used to attach to tick midgut by binding TROSPA protein on luminal side of tick gut epithelial cells
- in unfed ticks, expression of OspA and TROSPA are high
- during feeding, production of OspA decreases and OspC increases
- spirochete migrates to tick salivary glands where it can be passed to host
Function of OspC in lyme disease
- may help mediate attachment of bacteria to tick salivary glands, ready for transfer to mammalian host
- OspC also binds to tick salivary protein (Salp15) and coats bacteria with this tick protein
- salp15 is immunosuppressive in mammalian host
How is Salp15 immunosuppressive?
-protects bacteria from neutralizing antibodies in bloodstream of mammalian host
T/F: In mammalian host, Borrelia spirochete uses same set of surface molecules to bind to host cells and to ECM
-false
Early clinical manifestations of Lyme Disease
- Erythema migrans at site of tick bite
- rash appears 7-14 days after tick bite
- accompanied by fever, fatigue, headache, muscle ache
Spirochetes disseminate from site of tick bite in lyme disease by what 3 routes?
-cutaneous, lymphatic, and blood-borne routes
Signs of early disseminated Lyme Disease
- may appear days to weeks after solitary EM lesion
- secondary EM, muscle aches, fever, facial palsy, headaches, fatigue
Late Disseminated Lyme Disease
- may progress to this weeks or months later
- more commonly seen as intermittent swelling and pain of one or a few joints (often knee)
- may also cause neurological disease
What neurological disease may late disseminated Lyme Disease cause?
- Ataxia
- Memory loss
- Mood changes
- Sleep disturbances
4 ways B. burgdorfori persists in host
- protection from neutralizing antibodies via OspC/SalP15 interaction
- avoidance of complement-mediated killing by binding a HOST negative regulator of complement cascade (CRASP)
- antigenic variation of surface molecules
- hiding in immune privileged sites
CRASP and _______ interactions likely contribute to host range.
- factor H
- CRASP must not bind lizard Factor H and why lizard isnt host
Mechanism of antigenic variation of bacterial surface of B. burgdorfori
-VlsE (surface lipoprotein) undergoes antigenic variation by recombination of 15 silent cassettes into vlsE expression locus
2 methods to detect B. burdorfori in the host
- Cultivation: from vertebrate host or arthropod in Barbour-Stoenner-Kelly medium; slow grower needs 2-6 weeks; recovered from biopsy of EM, large vols of blood early in untreated disease, rarely CSF and NEVER from joint fluid
- PCR: can find evidence of organism in joint fluid using PCR
Diagnosis of Lyme Disease
- EM rash of 5 or more cm
- headache, muscle or joint pain IN SUMMER without respiratory or GI symptoms
- lab confirmation with ELISA followed by Western
Why are positive antibody tests not the best for detecting infection?
- take 1-2 weeks to make them
- cannot tell current infection or previous infection
Treatment of Lyme Disease
- Doxycycline for early localized or disseminated infection (Amoxicillin is 2nd choice)
- Intravenous antibiotic for late disseminated disease involving neurologic abnormalities
Why is treatment resistant arthritis following Lyme Disease treatment and eradication thought to be autoimmune?
- months or even several years AFTER antibiotic treatment
- PCR negative for organism in joint fluid
Rickettsia rickettsii structure and physiology
- gram negative, obligate intracellular pathogen
- causes rocky mountain spotted fever
Where and when do most cases of RMSF occur?
- Southeastern and South central states
- summer
Season occurrence of a diseases suggests what?
-vector spread illness
Vectors of RMSF
- West: wood tick
- East: dog tick
In the tick containing RMSF, bacteria are transmitted how?
- transovarially from mother to offspring in eggs
- takes pressure off of need to keep bacteria alive in nature
Rickettsia rickettsii bacteria are deposited on skin by feeding ticks and enter via ______.
-scratching
RMSF is characterized by what?
- sudden headache, fever, chills, muscle aches, and characteristic rash
- rash starts on periphery of body and spreads to the trunk
How is R. ricketsii spread throughout the body? Describe their interaction with host cells
- blood stream
- attach to vascular endothelial cells and induce their own uptake
- next, rapidly escape from vacuole and reach host cytosol where they replicate
- use localized polymerization of host actin to spread to adjacent cells or exit host by lysing finger-like projections
4 other intracellular bacteria that use actin polymerization to spread
- listeria
- shigella
- rickettsia
- vaccinia
RMSF treatment and prevention
- doxycycline (first choice) or chloramphenicol (second choice)
- no vaccine
- prevent by wearing protective clothing, using insect repellents, and by monitoring and promptly removing ticks
What is the cause of the plague
-Yersinia pestis
Structure and physiology of Yersinia pestis
- gram negative bacterium, baccilus
- primarily extracellular growth, but can grow in macrophages
- looks like safety pins in blood
What is the natural reservoir for Yersinia pestis? What is the vector?
- wild rodents
- main vector is rat flea
Transmission of Y. pestis from flea to mammalian host
- when flea bites rodent with plague, the bacteria multiple in gut of flea
- bacteria form biofilm that blocks the flea’s digestive tract so fleas cannot ingest more blood
- hungry fleas keep biting, each time regurgitating blood and some plague bacteria into the new bite wound and spreading Y. pestis
- *growth of of bacteria within flea vector alters the behavior of the fleas and aids in transmission of bacteria to mammalian host
As with all of these diseases today, humans are accidental hosts. What is the main host for Y. pestis?
-rats, but when they die from plague, feed on humans
Clinical disease of plague
- plague bacilli spread to LNs, causing them to swell and become hemorrhagic forming buboes
- accompanying fever, chills, headache, extreme exhaustion
If not treated immediately with antibiotics, Y. pestis can spread throughout bloodstream and produce _______.
- septicemic plague: systemic infection
- often fatal
What happens if Y. pestis invades lungs? what is now unique about transmission?
- cause pneumonic plague
- at this point, bacteria do not need fleas to spread and can be spread from humans to humans via airborne transmission
- creates very dangerous epidemic conditions
How does Y. pestis evade the immune system?
-prevents phagocytosis via capsule and TTSS effectors
TTSS of Y. Pestis: what are the effectors and what do they do?
- YopH, YopT, YopE, YopO
- prevent phagocytosis of bacterium by macrophages (disrupts host cytoskeleton)
- slows inflammatory response of host by decreasing INF gamma and TNF
How to diagnose the plague
-Giema or gram stain of smears from bulboes and/or blood
-fluorescent antibody test against unique envelope antigen
-
Treatment and prevention of the plague
- streptomycin or tetracycline
- isolate individuals with pneumonic plague
- rat control and insecticides
