Spirochetes and Vibrios

Question 1

spirochetes recurring themes

Answer 1

• wide variety of transmission methods
• cross easily into bloodstream
• primary virulence factors are for immune evasion- not immunogenic enough for a vaccine
• diagnosis is challenging-phases, treponema small, lyme no lab, eye exam is good
• little acquired antibiotic resistance-grow slowly and no plasmids
• Jarisch-Herxheimer reaction to treatment

Question 2

genera of spirochete pathogens

Answer 2

• treponema-syphilis, yaws, pinta
• leptospira-leptospirosis
• borrelia-lyme, relapsing fever

Question 3

T pallidium

Answer 3

• syphilis
• small-0.25 uM diameter means invisible to light microscope
• delicate, cant survive outside host
• motile-flagellar corkscrew motion
• human restricted in nature but can induce in lab rabbits
• cannot be grown in culture
• extremely infectious sexually
• virulence based on immune evasion

Question 4

t pallidum pathogenesis

Answer 4

• transmitted by sexual contact (acquired), blood, transplancentally (congenital)
• national plan to eliminate in US has hit bumps- MSM and SES disadvantaged

Question 5

acquired T pallidium

Answer 5

• penetrates mucous membranes or small abrasions
• grows in BV endo, enters lymphatics and bloodstream
• CNS is invaded relatively early, though symptoms take years to develop, first CSF abnormalities, then meninges, then parenchyma of brain and spinal cord
• host raises antibodies, but they aren’t useful
• surface of spirochete is nonimmunogenic
• spirochete downregulates TH1 cells

Question 6

primary syphilis

Answer 6

• painless chancre at site of transmission 3-6 weeks later- highly infectious
• IF infiltrate at site fails to clear organism
• chancre heals 3-12 weeks

Question 7

secondary syphilis

Answer 7

• 4-10 weeks, spirochete multiplication-systemic symptoms
• fever, malaise, myalgias, arthralgias, lymphadenopathy
• mucocutaneous lesions of variable types, condylomata lata, patchy alopecia (moth eaten)
• high antibody titers

Question 8

latent syphilis

Answer 8

• end for 2/3
• organism remains
• secondary symptoms resolve, may return intermittently over years

Question 9

tertiary syphilis

Answer 9

• 1/3 untreated, fatalities possible
• gummatous syphilis, granulomatous lesions with rubbery, necrotic center. primarily liver, bones, testes
• cardiovascular syphilis: >10 years: aneurysm of ascending aorta caused by chronic inflammation of vasa vasorum
• neurosyphilis

Question 10

neurosyphilis

Answer 10

• syphilitic meningitis-early -6mo
• meningovascular syphilis-damage to BV of meninges, brain, SC
• parenchymal neurosyphilis-tabes dorsalis- damage to SC- impaired sensation, wide based gait
• disruption of dorsal roots-loss of pain and temp sensation, areflexia
• general paresis-damage to cortical brain tissue-dementia

Question 11

Argyll Robertson pupil

Answer 11

• hallmark of neurosyphilis
• one or both pupils fail to constrict in response to light
• bur do constrict to focus on a near object

Question 12

congenital syphilis

Answer 12

• treponemes readily cross placenta and infect fetus
• miscarriage/stillbirth/neonatal death 40-50%
• within first two years, surviving infants develop sever secondary syphilis

Question 13

prevention of syphilis

Answer 13

-penicillin and CONDOMS

Question 14

B burgforferi bacteriology

Answer 14

• motile spirochete
• flat wave shape, not spiral
• stainable with giemsa, silver stain, IF, visible by standard microscopy
• tick borne, more common on east coast
• highest risk in summer, when nymphs are feeding
• small mammal reservoirs-mouse, rate perferred by nymphs, deer preferred by adults- can be in winter
• incidence increasing due to expansion of deer herds
• almost always requires 24h attachment to transmit

Question 15

removing ticks

Answer 15

• tweezers and gloves
• bag and freeze
• promptly
• doxy if patient is neither pregnant nor allergic to tetracyclines

Question 16

B burgdorferi pathogenesis

Answer 16

• disease begins with injection of b burdoferi into host by tick, asymptomatic clearance possible
• over next 6 months, organism spreads
• erythema migrans rash (75%), anti-spirochete/autoantibodies raised
• very persistent skin infection established
• months to 1 year after infection, immune/neurological issues arise (stage 2). lyme arthritis predisposed by HLA-DR4 and HLA-DR2 genotypes and strains of bacteria
• other strains associated with neuro manifestations
• post lyme- 80% of untreated/undertreated cases report some neurological sequela
• reinfections occur

Question 17

exam

Answer 17

• pt usually doesn’t recall tick bite, get history of outdoor activity, note season and geographic location
• stage 1- erythema migrans expanding rashes at or near bite site, bulls eye appearance in a minority
• rash around still attached tick is likely to be hypersensitivity, not Lyme
• flu like constitutional symptoms, fatigue, muscle ache, regional lymphadenopathy, low fever
• coinfection with erlichia or babesioa-high fever

Question 18

stage 3

Answer 18

• chronic lyme
• arthritis
• subacute encephalopathy
• chronic progressive encephalomyelitis
• late axonal neuropathies
• fibromyalgia
• may recall earlier episodes of bell palsy or aseptic meningitis

Question 19

lab for lyme

Answer 19

• serology, ELISA, and IFA can confirm exposure to b burgdorferi, but not until 6-8 weeks later
• patients who received briefly available vaccine will be seropositive
• seropositivity remains long term, not useful for testing the cure or comparing acute w/ convalescent sera
• urine antigen testing is in pipeline

Question 20

treatment

Answer 20

• empiric is ok if have history/seropositive/not preg
• treat pts with erythrema migrans
• 10-20 days with doxy unless preg or allergic
• if symptoms are equivocal, may observe rash 2-3 days, erythema migrans will expand
• or treat and look for Jarisch Herxheimer reaction

Question 21

lyme prevention

Answer 21

• protective clothing, deet, avoid woodsy areas, tick collars
• inspection
• prophylaxis with doxy in some geographic areas

Question 22

vibrio recurring themes

Answer 22

• curved, gram neg rods
• mostly ocean dwelling
• several are halophiles
• primarily cause fecal-oral gastroenteritis
• can also infect wounds contaminated by seawater or ocean debris
• also peptic ulcers
• gastroenteritis and peptic ulcers require specialized virulence factors for survival in the GI

Question 23

V cholerae bacteriology

Answer 23

• curved, comma shaped, motile gram neg rod
• stains aerobic, facultatively anaerobic
• microscopic discovery of Robert Koch
• has been causing human epidemics for at least a millennium
• epidemic in london in 1854: john snow and the broad street pump
• 2 reservoirs-humans and plankton ecosystem of indian ocean

Question 24

V cholerae pathogenesis

Answer 24

• transmitted fecal oral
• shed by asymptomatic carriers in incubation of convalescence
• travels to untreated water or undercooked shellfish
• usually killed by stomach acid
• high ID50- 1000-1 mil
• people on antacids or with gastrectomy are more susceptible
• surviving bacteria reach small intestine, secrete mucinase to clear path to brush border, attach and colonize

Question 25

V cholerae pathogenesis 2

Answer 25

• growing bacteria secrete cholera toxin (enterotoxin)-cholderagen
• AB subunit structure
• persistent activation of adenylate cyclase, loss of water and ions
• blocks absorption by microvilli while also promoting secretion from crypt
• massive watery diarrhea
• toxin and virulence factors carried by lysogenic phage CTX

Question 26

V cholerae pathogenesis 3

Answer 26

• local acting, little penetration of the gut wall
• morbidity and death result from dehydration and electrolyte imbalance, severe cases may kill in hours
• surviving patients run the self limited course in 7 days

Question 27

v cholerae diagnosis

Answer 27

• mild dehydration-3-5% down from normal body weight, excessive thirst
• moderate-5-8%, hypotension, tachycardia, weakness, fatigue, prolonged skin tenting, acidosis
• severe-10%, glassy/sunken eyes, sunken fontanelles in infants, pulse weak/thready/absent, wrinkled skin, can’t wake up, coma
• difficult to catch in child

Question 28

V cholerae treatment

Answer 28

• rehydrate and rebalance electrolytes

- treat with short course tetracycline, doxy, or furazolidone after IV rehydration to shorten course and reduce shedding

Question 29

H pylori

Answer 29

• discovered in 1893
• curved gram neg rods
• similar to campylobacter, but strongly urease pos
• causes peptic ulcer disease, associated with mucosa associated lymphoid tissue (MALT) lymphomas, gastric lymphoma, adenocarcinoma of stomach

Question 30

h pylori pathogenesis

Answer 30

• transmission mode unknown, probably person to person within households
• bacteria attach to mucous secreting cells of stomach with flagella virulence factor
• break down urea to ammonia with urease virulence factor
• ammonia neutralizes stomach pH, allowing bacterial growth and irritating stomach lining
• organism appears to create a niche in the lining where it multiplies, leads to immune infiltrate
• appears to upregulate caspases, causing apoptosis in nearby cells
• irritation predisposes to gastritis, peptic ulcer, gastric cancer and MALT lymphoma

Question 31

H pylori diagnosis

Answer 31

• culture is difficult and not useful
• urea breath-drink radioactive urea and breath pos co2 if pos
• antigen present in stool-tests are becoming available but are expensive

Question 32

h pylori treatment

Answer 32

• reduce irritation/ pain/ help ulcers heal with bismuth salts and proton pump inhibitors
• kill bacteria with one of three triple therapies:
• omeprazole amox and clarithrymycin for 10 days
• bismuth subsalicyclate, metronidazole, tetra for 14
• lansoprazole, amox, clarithromycin for 10
• reinfection may occur