Gram Negative: Spirochetes

Question 1

What are spirochetes? What are some of their major features?

Answer 1

• these are small corkscrew shaped Gram negative organisms
• they have unique periplasmic flagella that result in a spinning movement
• they have a unique 4th layer outside of the lipid bi-layer with LPS; this is made up of phospholipids and contains very few exposed proteins (this helps the organism hide from the immune system)

Question 2

What are periplasmic flagella?

Answer 2

• these are flagella unique to spirochetes
• they run along the organism within the outer membrane rather than protruding from the membrane
• movement of these flagella results in a spinning movement of the spirochetes

Question 3

What are the three genera of the spirochetes? Which diseases does each cause?

Answer 3

• Treponema: syphilis (also bejel, yaws, and pinta)
• Borrelia: lyme disease, relapsing fever
• Leptospira: leptospirosis, Weil’s disease

Question 4

How do treponemes cause disease? What is the main pathogen and what disease does it cause?

Answer 4

• Treponema lack toxins or destructive enzymes
• disease is actually caused by the body’s own immune response (inflammatory infiltrates, vascular proliferations, granulomas, etc.)
• major pathogen is Treponema pallidum, which causes the STD syphilis

Question 5

What is syphilis? Which population is at high risk? What is the pathogenic course of syphilis?

Answer 5

• syphilis is an STD caused by Treponema pallidum
• high risk group: MSM (men who have sex with men); 60% of syphilis patients fall into this category
• syphilis has a primary stage followed by a secondary stage and then a tertiary stage; there is a latent period between the 2nd and 3rd stages

Question 6

Primary Syphilis

Answer 6

• primary syphilis is the 1st stage of this disease
• characterized by painless chancre (ulceration) at the site of inoculation 3-6 weeks after initial contact with the organism
• painless regional lymphadenopathy also occurs
• the chancre lesion is constantly shedding organisms and is therefore highly contagious
• this stage of syphilis resolves after about 4-6 weeks, and leaves NO scar; if untreated it is followed by secondary syphilis

Question 7

Secondary Syphilis

Answer 7

• this is the 2nd stage of the disease
• it occurs about 6 weeks after the primary chancre (ulcerative lesion) heals
• characterized by a systemic bacteremia: widespread rash, generalized lymphadenopathy, multi-organ involvement, weight loss, fever, etc.
• this resolves after about 6 weeks and is followed by a latent stage of disease

Question 8

What rash/skin changes occur in secondary syphilis?

Answer 8

• this widespread rash consists of small red lesions that tend to be more prevalent on the palms and soles and in the oral cavity
• there may also be a wart-like lesion on the vulva or scrotum called condyloma latum (like the chancre in primary syphilis, this lesion is highly contagious)

Question 9

Latent Phase of Syphilis

Answer 9

• this follows resolution of secondary syphilis
• it is largely asymptomatic, although serology will remain positive
• 25% will experience relapses of secondary syphilis during this latent phase

Question 10

What percentage of patients in the latent phase of syphilis will become non-infectious? What percent will develop tertiary syphilis? Which population is always at risk of contracting the infection even when dealing with patients who fall into the first category?

Answer 10

• 2/3 will remain asymptomatic and become non-infectious
• however, pregnant woman in this group can still pass the infection onto their fetuses!
• the remaining 1/3 will go on to slowly develop tertiary syphilis over the next 6 to 40 years

Question 11

Tertiary Syphilis

Answer 11

• this stage of the disease follows the latent period in 1/3 of patients
• it is characterized by a slow accumulation of inflammatory damage that can develop anytime 6 to 40 years from the latent stage
• there are 3 categories of this stage: gummatous (15% of cases), cardiovascular (10%), and neurosyphilis (8%)

Question 12

What characterizes the gummatous type of tertiary syphilis?

Answer 12

• this type occurs in 15% of cases of tertiary syphilis
• it develops between 3 and 10 years after the initial primary infection
• consists of gummas (granulomas that necrose and become fibrotic) in the skin and bones
• (skin gummas tend to be painless, while those in the bone tend to have a deep gnawing pain)

Question 13

What characterizes the cardiovascular type of tertiary syphilis?

Answer 13

• this type occurs in 10% of cases of tertiary syphilis
• it develops at least 10 years after the initial primary infection
• consists of aneurysms in the ascending aorta and aortic arch; due to inflammatory destruction of the vasa vasorum (the vessels that supply the aorta), leading to a weakened and necrotic media layer

Question 14

What characterizes the neurosyphilis type of tertiary syphilis?

Answer 14

• this type occurs in 8% of cases of tertiary syphilis
• it has several presentations: asymptomatic (but CSF contains syphilis), subacute meningitis (CSF shows more lymphocytes than neutrophils), meningovascular syphilis (damage to neuro vasculature causing occlusion and infarction in nerve tissue), tabes dorsalis (damage to dorsal columns and dorsal roots of spinal cord), general paresis (progressive mental deterioration)

Question 15

What is subacute meningitis? Which organisms cause it?

Answer 15

• subacute meningitis is a less threatening and more gradual development of meningitis
• it is characterized by an elevation in lymphocytes, rather than neutrophils, in the CSF
• Treponema pallidum (syphilis) and Mycobacterium tuberculosis cause this type of meningitis

Question 16

What is Argyll-Robertson pupil? What is it also known as?

Answer 16

• this clinical sign may be seen in patients suffering from neurosyphilis (a presentation of tertiary syphilis) in the form of tabes dorsalis and general paresis
• the patient’s accommodation reflex is in tact, but there is no pupil reaction to light
• AKA “prostitute’s pupil”

Question 17

What is the “rule of 6’s” when it comes to syphilis?

Answer 17

• Treponema pallidum has 6 axial filaments (periplasmic flagella)
• 6 week incubation period
• 6 weeks for the initial ulcer to heal
• 6 weeks after healing for secondary syphilis to develop
• 6 weeks for secondary syphilis to resolve
• 66% of latent stage patients will have resolution (remaining 1/3 will develop tertiary syphilis)
• (at least) 6 years to develop tertiary syphilis (6 to 40 years)

Question 18

What is congenital syphilis? What is early congenital syphilis? Late congenital syphilis?

Answer 18

• congenital syphilis occurs when Treponema pallidum crosses the placental blood barrier; it is has a high mortality rate
• those that survive nearly always develop either early or late congenital syphilis
• early: occurs within 2 years; resembles a severe secondary syphilis; patient develops widespread rash, condyloma latum, and a very runny nose
• late: occurs after 2 years; resembles tertiary syphilis (but without the cardiovascular involvement); patients develop CN VIII deafness, bone and teeth deformities, and eye disease

Question 19

At which point of gestation does Treponema pallidum start to harm the fetus?

Answer 19

• T. pallidum doesn’t harm the fetus until the 4th month of gestation
• this means we have a decent window period in which we can give the mom antibiotic therapy to prevent congenital syphilis

Question 20

What is the Jarish-Herxheimer Phenomenon? What is it caused by?

Answer 20

• this is a self-limiting reaction characterized by mild fever, chills, malaise, headache, and muscle aches
• it is an initial response to antibiotic therapy for syphilis (and can occur in the treatment of any spirochetes)
• it is due to the killed organisms releasing pyrogens

Question 21

Which three subspecies of Treponema pallidum are non-neveneral? Which disease does each cause and where are they found?

Answer 21

• T. pallidum endemicum: causes bejel (endemic syphilis in desert zones of Africa and the Middle East); oral mucosa is commonly affected first
• T. pallidum pertenue: causes yaws (a disease found in tropical areas); often disfigures the face
• T. pallidum carateum: causes pinta (found in rural Latin America); purely a skin discoloration disease with an eruption of red lesions that turn blue in sunlight

Question 22

What is lyme disease? How is it transmitted? What is the pathogenic course of lyme disease?

Answer 22

• lyme disease is the most common tick-borne illness in the U.S. and is caused by the spirochete Borrelia burgdorferi
• it is very similar to syphilis, but is NOT sexually transmitted
• the spirochete is transmitted via insect vectors
• has 3 stages (like syphilis): early localized, early disseminated, and late stage

Question 23

Which insect vector carries Borrelia burgdorferi? How long does the transmission require? Which animals are the reservoirs of this insect?

Answer 23

• lyme disease is transmitted via the Ixodes tick bite
• the transfer requires at least 24 hours for the spirochetes to enter the host (make sure to check for ticks during this window period!)
• the reservoirs are mice and deer

Question 24

Early Localized Stage of Lyme Disease

Answer 24

• the 1st stage of lyme disease
• occurs about 10 days after the initial bite and lasts for about 4 weeks
• characterized by a skin lesion that develops at the bite site (erythema chronicum migrans: a red round rash that spreads out from the site), flu-like illness, and regional lymphadenopathy

Question 25

Early Disseminated Stage of Lyme Disease

Answer 25

• the 2nd stage of lyme disease (but can also occur at the same time as the 1st stage)
• Borrelia burgdorferi spread to the skin, nervous systems, heart, and joints
• characterized by multiple skin lesions (multiple erythema chronicum migrans), meningitis/CN palsies/etc, heart block/myocarditis (often transient), and migratory arthritis

Question 26

Late Stage of Lyme Disease

Answer 26

• the 3rd stage of lyme disease
• this occurs in about 10% of untreated patients
• characterized by chronic arthritis and potential chronic neurologic damage

Question 27

What is relapsing fever? How is it transmitted? What is the pathogenic course?

Answer 27

• relapsing fever is caused by the spirochete Borrelia recurrentis
• it is transmitted via the body louse
• the organism enters the blood and causes high fever, chills, headaches, and muscle aches that all resolve after 3 to 6 days, but then return after another 8 days (this cycle repeats, and the relapses shorten each time)
• this relapsing and remitting is a result of rapid antigenic variation

Question 28

What is leptospirosis? How is it transmitted? What is the pathogenic course?

Answer 28

• leptospirosis is caused by the spirochete Leptospira
• the organism is found in the urine of animals and can penetrate abraded skin and mucous membranes (most commonly, it is transmitted by swallowing infected water while swimming)
• the disease has an initial leptospiremic phase followed by a short afebrile period and then the secondary immune phase

Question 29

Leptospiremic Phase of Leptospirosis

Answer 29

• this is the 1st phase of leptospirosis
• the Leptospira spirochetes invade the blood and CSF causing an abrupt high fever, headache, malaise, and severe muscle aches (especially in the thighs and back)
• patients also develop red conjunctiva and photophobia
• this phase lasts about 1 week

Question 30

Immune Phase of Leptospirosis

Answer 30

• this is the 2nd phase of leptospirosis
• this is a recurrence of symptoms that follows a short afebrile period after the initial leptospiremic phase
• symptoms are the same as the leptospiremic phase (fever, headache, malaise, muscle aches of thighs and back)
• it is called the immune phase because it correlates with the emergence of IgM antibodies

Question 31

What is Weil’s disease?

Answer 31

• this is a more severe disease caused by Leptospira (usually it causes leptospirosis)
• it is characterized by infectious jaundice with renal failure, hepatitis, mental status changes, and organ hemorrhage

Question 32

How do we treat syphilis? Lyme disease? Leptospirosis?

Answer 32

• syphilis: penicillin (also heat, drying, soap and water); penicillin also crosses the placental barrier, and so can also cure congenital syphilis
• lyme disease: penicillin or doxycycline
• leptospirosis: treat immediately when suspected with penicillin or doxycycline