Lecture 17 Spirochete

Question 1

What are all the types of Spirochaetaceae?

Answer 1

• Spirochaeta (water, marsh, springs)
• Cristispira (mollusks)
• Treponema (termites)
• Borrelia (Lyme disease)
• Leptospira (Free-living)
• Brachyspira (dysentery in pigs, chickens, human intestine)

Question 2

What are the families of Spirochetes?

Answer 2

• Spirochaetaceae
• Leptospiraceae
• Brachyspiraceae

Question 3

What are the pathogenic spirochetes?

Answer 3

• Treponema (syphilis, periodontal disease, normal flora)
• Borrelia (lyme disease, relapse fever)
• Leptospira (leptospirosis)

Question 4

What is the structure of spirochetes?

Answer 4

• Corkscrew shaped
• The genera vary in terms of length and thickness;
Leptospira have hooked ends
• Lipid-rich outer membrane covering periplasmic flagella; thin peptidoglycan layer covering cytoplasmic membrane

Question 5

Which pathogenic spirochetes have small genomes?

Answer 5

-Borrelia, Treponema pallidum

Question 6

Borrelia has what type of DNA structures?

Answer 6

• linear chromosome

- linear and circular plasmids

Question 7

What are Leptosira chromosomes like?

Answer 7

-2 circular chromosomes

Question 8

Which pathogens have high genetic variability?

Answer 8

• Borrelia

- Leptospira

Question 9

What is unique to Treponema pallidium?

Answer 9

Cannot be grown in vitro, has high G+ C in comparison to other spirochetes

Question 10

Which organisms cause Relapsing fever?

Answer 10

–Borreliarecurrentis: louse-borne

–Borreliahermsii: tick-borne

Question 11

What are the habitats for Relapsing fever causing organisms?

Answer 11

–Tick-borne: Reservoirissquirrelsandothersmall
rodents.
– Louse-borne: Person-to-person transmission via louse. No known animal reservoir.

Question 12

How is relapsing fever transmitted?

Answer 12

• Tick borne (B. hermisii) infects tick tissues, infects human by sailiva or feces during bite
• Louse borne (human infection) no invasion of louse tissue. Humans are infected by hemolymph when tick is crushed

Question 13

What is the clinical course of relapsing fever?

Answer 13

• Incubation period: 7 days
• Sudden onset of fever (40oC), headache, pain
in muscle, bones, joints
• Recurrent periods of fever (spirochetemia: 107-8/ml blood), interrupted by afebrile periods

Question 14

What is the pathogenesis of relapsing fever?

Answer 14

• Gene conversion and antigenic variation.
• New serotypes appear, each new one overgrowing due to the selective advantage against the old serotypes (antibodies made for old)

Question 15

How do relapssing fevers utilize antigenic variation?

Answer 15

• Classic example of antigenic variation of surface variable membrane proteins (21-39 Kd)
• Vmp’s are now divided into Vlp and Vsp; ~30 genes.
They are located on a linear plasmid and are silent, through gene conversion they recombine.

Question 16

What makes Borrelia so invasive?

Answer 16

-It can infect many tissues and organ systems, including the central nervous system (vsp allele)

Question 17

What is dx and rx of Relapsing fever?

Answer 17

• Clinical features
• Blood films during fever crises - large
numbers of spirochetes in blood 
• Treatment
–Penicillins, tetracyclines

Question 18

Which organisms cause Lyme disease?

Answer 18

◦ Borrelia (Borreliella?) burgdorferi – high heterogeneity in outer surface proteins: OspA, OspB, OspC
◦ Other related Borrelia species identified: B. garini, B. afzeli, B. lonestari (?)

Question 19

What is the habitat for Lyme disease causing organisms?

Answer 19

– Major reservoir in nature is in small rodents,
deer
– Transmitted to humans via tick bite (incidental infection)

Question 20

How is lyme disease transmitted?

Answer 20

• Transmitted by Ixodes ticks
• Human infection usually occurs by bite of a nymph looking for a blood meal
• Prevalence of infected ticks: varies by geographic region

Question 21

What is the pathogenesis of lyme disease?

Answer 21

• Injected into skin from tick saliva
• Slow transmission to mammal—>24 hours
• Different antigens expressed in tick versus mammal (more OspC in mammals)

Question 22

What occurs once the lyme disease pathogen is in the body?

Answer 22

• Organism is very invasive, reaches blood stream and disseminates to many organs, including central nervous system
• Persistent, chronic infection
due to antigenic variation

Question 23

What is the clinical course for Lyme disease?

Answer 23

1. Eyrthema chronicum migrans (ECM) and secondary lesions
2. Neurologic and cardiac abnormalities (HA, stiff neck, conjunctivitis, muscle pain weeks to months after)
3. Arthritis (weeks to year, intermittent or chronic)

Question 24

How is Lyme disease dx?

Answer 24

• Physical exam - (ECM or hx)
• biopsy (cx or staining)
• serologic test-not reliable
• DNA detection - PCR

Question 25

How is lyme disease treated?

Answer 25

* Penicillin, ceftriaxone, tetracyclines * Treatment of ECM is effective * Later treatment may not be successful: chronic inflammation in absence of bacteria (Autoimmunity?) * New evidence for persistence of viable Bb after antibiotic treatment

Question 26

What is syphilis?

Answer 26

-Disease caused by Treponema pallidum • Chronic bacterial infection, sexually transmitted • Early manifestations involve primarily skin • Late manifestations involve virtually all organs and tissue sites

Question 27

What is the shape of Treponema pallidum?

Answer 27

– Corkscrew-shaped, microaerophilic, noncultivable bacterium, 10-14 μ in length, 0.5 μ in diameter

Question 28

What is the habitat for Syphilis organism?

Answer 28

• Habitat | — Human only (? higher primates)

Question 29

What is important about the metabolism of Treponema pallidum?

Answer 29

— Highly dependent on host cells — No pathways for synthesis of fatty acids, nucleotides, amino acids — No Kreb’s cycle, no respiratory electron transport chain

Question 30

How is syphilis transmitted?

Answer 30

- Direct, usually sexual (infectious at 1 or 2 stage) - Highly invasive, gains access to blood stream and disseminates (CNS included) - May also cross placenta to cause congenital syphilis

Question 31

What is the natural history of untreated syphilis?

Answer 31

- Infection (incubation 2-4 weeks) - Primary (heals spontaneously) - secondary (rash, enlarged lymph nodes of body - Latent (lead to lifetime latency or tertiary) - Tertiary (aortic destruction, Gumma, CV syphilis, tabes dorsalis, paresis)

Question 32

What is congenital syphilis?

Answer 32

- infection of fetus during pregnancy | - Results in prematurity, spont abortion, stillbirth, neonatal or death, latent infection

Question 33

What is the pathogenesis of syphilis?

Answer 33

- immune response clears primary and secondary lesions, but not systematically - lifelong, chronic if untreated - maybe identify surface proteins - Some putative OMPs bind fibronectin, laminin, fibrinogen

Question 34

What accounts for the persistent secondary stage of syphilis?

Answer 34

-TprK -7 variable regions -evade immune system 0antigenic variation by gene conversion -one expression site, more than 50 variable

Question 35

How is syphilis dx?

Answer 35

- dark field microscopy - no cx possible - PCR, RT-PCR not commercially available - Serological testing

Question 36

How is syphilis treated?

Answer 36

* Penicillin –first line * Alternatives: Doxycycline, tetracycline * Macrolides – recently discovered resistance

Question 37

What organism causes Leptospirosis?

Answer 37

–Leptospira interrogans –Many strains have been described –Taxonomy is unclear –Pathogens considered to be one species with up to 300 serovars

Question 38

What is the habitat of Leptospirosis?

Answer 38

``` • Most widespread zoonosis in the world • Animal reservoir • Both domestic and wild animals • Infection rate in raccoons, opossums, skunks ranges from 10-50% • Change in epidemiology – urban slums with rats ```

Question 39

How is Leptospirosis transmitted?

Answer 39

Leptospirosis: Transmission • Source of infection is water contaminated with the infected urine of “carrier” animals • Portal of entry is skin, mucous membranes • Teenagers, young adults at highest risk of infection • Carrier state persists for months to years • Even in inapparent infection, bacterial load may reach 1010/gram of tissue in kidneys

Question 40

Leptospirosis infection is..

Answer 40

- highly invasive | - disseminates to infect multiple organisms

Question 41

What are clinical outcomes of leptospiral infection?

Answer 41

Few- complex, multi-system disease Some- undifferentiated fever Most- inapparent infection

Question 42

What are some complex Leptospiral infections?

Answer 42

``` Aseptic meningitis Renal failure Jaundice Myocarditis Pulmonary hemorrhage Refractory shock ```

Question 43

What is the clinical course of Leptospirosis?

Answer 43

• 7-10 day incubation period • Sudden onset of fever (spiking), severe myalgia, headache • Bacteria present in blood, CSF, urine • Usually self-limited, but can be protracted and severe

Question 44

How is Leptospirosis dx?

Answer 44

• Culture: Blood, CSF - Early Urine - Chronic • PCR is available • Serology: Useful in later infection

Question 45

How is Leptospirosis treated?

Answer 45

* Penicillin, doxycycline, erythromycin * 7% mortality overall, higher in older persons * 15-48% mortality for icteric form