Spirochetes and Vibrios Flashcards
1
Q
Recurring themes of spirochetes
A
- wide variety of transmission methods
- cross easily to blood stream, some also cross blood-brain barrier
- primary virulence factors are for immune evasion
- diagnosis is challenging
- once correctly diagnosed, treatment may be simple
- Jarisch-Herxheimer reaction to treatment
2
Q
Spirochetes- wide variety of transmission methods
A
- Sexual: syphilis
- Vector: Lyme Disease, relapsin fever
- Environmental: Leptospirosis
3
Q
Spirochetes- primary virulence factors are for immune evasion
A
- little inflammation: no Brudzinki’s sign
- few exotoxins
- no vaccines
4
Q
Spirochetes; Diagnosis is challenging
A
-wide variety of symptoms: disease develops in phase as spirochetes invade new organs; meticulous history-taking is crucial to accurate diagnosis
-T. palludum (symphilis) are too small to see by standard microscopy
-B. burgdorfi (Lyme Disease) has no good lab diagnostic
-Eye exam can be useful:
Argyll-Robertions pupil
Conjunctival suffusion, uveitis in leptospirosis
5
Q
Jarisch-Herxheimer reaction to treatment
A
- Occurs 24 hr after antibiotic treatment
- flulike symptoms
- lasts 24-48 hrs
6
Q
Genera of Spirochete Pathogens
A
- TreponemaL Syphilis, yaws, pinta
- Leptospira: Leptospirosis
- Borrelia: Lyme Disease, relapsin fever
7
Q
T. pallidum Bacteriology
A
- Small: 0.25uM diameter means invisible to light microscope, need dark field
- delicate: can’t survive outsite host
- motile: flagellar “corkscrew” motion
- human-restricted in nature (can infect rabbits in lab)
- cannot be grown in culture
- extremely infectious sexually
- virulence based on immune evasion
8
Q
Overview of T. pallidum
A
- transmitted by sexual contact (aquired), blood transplacentally (congenital)
- national plan to eliminate in US has hit bumps: MSM and socioeconomically disadvantaged
9
Q
Acquired T. Pallidum
A
- T. pallidum penetrates mucous membranes or small abrasions, grows in blood vessel endothelium, 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: specific anti-treponemal, nonspecific reagin
- But immunity is incomplete:
- surface of spirochete is nonimmunogenic
- spirochete down regulates TH1 cells
10
Q
Primary syphilis
A
- painless chancre at site of transmission 3-6 weeks later:highly infectious
- inflammatory infilitrate at site fails to clear organism
- chancre heals 3-12 weeks
11
Q
Secondary syphilis
A
- 4-10 weeks, spriochete multiplication -> systemic symptoms
- fever, maliase, myalgias, arthralgias, lymphadenopathy
- mucocutaneous lesions of variable types, condylomata later, patchy alopecia (“moth eaten”)
- high antibody titers
12
Q
Latent syphilis
A
- end for 2/3
- organism remains
- secondary symptoms resolve, may reutrn intermittently over years
13
Q
Tertiary Syphilis
A
- 1/3 untreated, fatalities possible
- gummatous syphilis: granulomatous lesions (“gummas”) with rubbery, necrotic center. Primarily liver, bones, testes
- Cardiovascular syphilis: (>10 years): aneurysm of ascending aorta causes by chronic inflammation of vasa vasorum
- Neurosyphilis
14
Q
Neurosyphilis
A
-syphilitic meningitis: early 6 mon
-mengingovascular syphilis: damage to blood vessels of meninges, brain, spinal cord
-parenchymal neurosyphilis:
Tabes dorsalis- damage to spinal cord-> impaired sensation, wide-based gait
Disruption of dorsal root-> loss of pain and temperature sensation, areflexia
General paresis: damage to cortical brain tissue -> dementia
15
Q
Neuosyphilis signs
A
- Argyll-Robertson pupil: Hallmark of neurosyphilis
- one or both pupils fail to constrict in response to light
- but does constrict to focus on a near object
16
Q
Congenital Syphilis
A
- treponemes readily corss placenta and infect fetus
- misscarriage/stillbirth/neonatal death 40-50%
- within first two years, surviving infants develop severe secondary syphilis
17
Q
Treatment of Syphilis
A
- single injection of penicillin for primary or seconday. Slow release
- use condoms
18
Q
Borrelia burgdorferi (Lyme Disease) Bacteriology
A
- motile spirochete- flat-wave shape, not spiral
- stainable with giema, silver stain, visible by standard microscopy
- tick borne- more common in East Coast
- highest risk in summer, when nymphs are feeding
- small mammal reservoirs for nymphs, large mammal hosts by adults
- incidence in US increasing due to expanision of deer herds
- almost always takes 24 hr attachment to transmit
19
Q
Removing ticks
A
- tweezers, gloves
- bag and freeze
- promptly (Lyme requires 24-48 h to transmit)
- Doxycycline if the patient is neither pregnant nor allergic to tetracyclines
20
Q
B. burgdorferi pathogenesis
A
- disease begins with injection of B. burdorferi into host by tick. Asymptomatic clearance possible
- over the next 6 mon, organism spreads, erythema migrans rash (75%), anti-spirochete/autoantibodies raised
- months to 1 yr after infection, immune and/or neurological issues arise
- lyme arthritis predisposed by HLA-DR4 and HLA-DR2 genetypes
- post-lyme: 80% of untreated/undertreated cases report some neurological sequela
- reinfections occur
21
Q
B. burgdorferia Exam
A
- patient usually does not recall tick bite- get history of outdoor activity, note season and geographic location
- stage 1: erythema migrans expanding rash(es) at or near bite site, bull-s eye appearance in minority
- rash aroud a still-attached tick is likely to be hypersensitivity, not Lyme
- Flulike constitutional symptoms, fatique, muscle ache, regional lymphadenopthy, low fever
- coinfection with erlichia or babesioa: high fever
22
Q
Chronic Lyme Disease
A
- Stage 3
- arthritis
- subacute encephalopathy
- chronic progressive encephalomyelitis
- late axonal neuropathies
- fibromyalgia
- patient may recall earler episodes of Bell palsy, aseptic meningits
23
Q
B. burgdorferi Lab Diagnosis
A
- Serology, ELISA and IFA can confirm exposure but not until 6-8 weeks later
- vaccinated will be seropositive
- seropositively remains longterm
- urine antigen testing is in the pipeline
24
Q
B. burgdorferi Treatment
A
- treat patients who present with erythema migrans
- attempt empiric treatment of patients who are seropositive with other suggestive symptoms/history unless pregnant.
- treat 10/20 days with doxycycline unless pregnant or allergic
- Jarisch-Herxheimer reaction
25
Q
B. burgdorferi Prevention
A
- Avoidance- protective clothing, DEET, avoid woodsy areas, tick collars on pets
- inspection: daily close inspection of whole family (including pets) for ticks during outdoor season
- prophylaxis with doxycycline may be recommended in some geographic areas
26
Q
Vibrios- shape
A
- curved, gram- rods
- mostly ocean-dwelling
- several are halophiles (like salt water)
27
Q
Vibros- causes of infection
A
- primarily cause fecal oral gastroenteritis
- can also infect wounds contaminated by seawater or ocean debris
- also peptic ulcers
28
Q
Specialized virulence factors of vibrios
A
-gasoenteritis and peptic ulcers require specialized virulence factors for survival in the GI
29
Q
Vibrio chloerae Bacteriology
A
- curved, comma-shaped motile gram(-) rod
- strains aerobic, facultatively anaerobic
- microscopic discovery of Robert Koch
- has been causing human epidemics for at least a millenium
- epidemic in London in 1854: Broad street pump
- 2 reservoirs: humans and plankton ecosystem of Indian ocean
30
Q
V. cholerae pathogenesis
A
- transmitted by fecal oral route
- shed by asymptomatic carriers in incubation or convalescence
- travels to untreated water or undercooked shellfish
- usually killed by stomach acid: high infectious dose (1000-1,000,000 IUs), people on antacids or with gastrectomy are most susceptible
- surviving bacteria reach small intestine, secrete mucinase to clear path to brush border, attach and colonize
- growing bacteria secrete chlorea toxin (enterotoxin): choleragen
- A-B subunit structure
- B binds the ganglioside receptor GM1 on intestinal lining
31
Q
Persistant activation of V. chlorae
A
- B binds to receptor and A cause persistent activation of adenylate cyclase, leads to loss of water and ions
- blocks absorption by microvilli while also promoting secretion from crypt
- leads to massive watery diarrhea
- toxin and other virulence factors carried by lysogenic bacteriophage CTX
- local-acting, little penetration of gut wasll
- morbidity and death result from dehydration and electrolyte imbalance
- surviving patients run the self-limited course in 7 days
32
Q
Exam of V. chlorae
A
- Rice water stool
- no pain, blood or neutrophils in stool
- acidosis and hypokalemia from loss of bicarbonate and potassium
- dehydration leading to cardiac and renal failure, 40% untreated mortality
- look for dehyration in hand skin
33
Q
Treatment of V. cholerae
A
- rehydrate and rebalance electrolytes
- treat with a short course of tetracycline, doxycline, or furazolidone after IV rehydration to shorten course and reduce shedding
34
Q
Helicobacter pylori bacteriology
A
- discovered in 1983
- curved gram(-) rods
- very similar to Campylobacter, but strongly Urease (+)
- causes peptic ulcer disease, associated with mucosa- associated lymphoid tissue (MALT) lymphomas, gastric lymphoma, adenocarcinoma of the stomach
35
Q
Pathogenesis of H. pylori
A
- transmission mode is known, probably person to person
- bacteria attach to mucus-secreting cells of stomach
- break down urea into ammonia w/ urease virulence factor
- ammonia neutralizes stomach pH, allowing bacterial growth and irritating stomach lining
- organisms appears to create a niche in the lining where it multiples
- appears to upregulate caspases, causing apoptosis in nearby cells
- irritation predisposes to gastrisis, peptic ulcer, gastric cancer, and MALT llymphoma
36
Q
H. pylori Diagnosis
A
- culture is very difficult, and not useful
- “Urea breath” test” : patient ingests radiolabeled urea, if infected, exhales radiolabeled carbon dioxide
- antigen present in stool, tests for it are becoming available but expensive
37
Q
Treatment of H. pylori
A
- reduce irritation with bismuth salts (Pepto Bismol)
- proton pump inhibitors
- kill bacteria with metronidazole+ amoxicillin or tetracycline for 10-14 days
- reinfection may occur
