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Spirochetes

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What are the 3 Spirochetes and the diseases they cause?
3 INVASIVE species of spirochetes:

1) Treponema pallidum = syphilis

2) Borrelia burgdorferi = Lyme disease

3) Leptospira interrogans = leptospirosis (anicteric or icteric)
How is syphilis transmitted?
sexually

T. pallidum cannot survive outside of human hosts
What are the stages of syphilis?
1) Incubation (3-90 days, median 21 days)
2) Primary
3) Secondary
4) Latent
- Early Latent
- Late Latent
5) Tertiary/Late
- Gummatous / Late Benign
- Cardiovascular
- Neurosyphilis
Describe the primary syphilis.
Chancre = raised borders, painLESS, single lesion in a genital area
What are the exceptions of primary syphilis?
Exceptions to the rule: Lesions of primary syphilis can be painful (especially if superinfected), multiple lesions, in an extragenital location
Describe secondary syphilis.
The lesions of secondary syphilis usually begin on the trunk and proximal extremitites as bilateral, pink to red, discrete macular lesions 3-10mm in diameter.

Targetoid shaped lesions, can also be on palms and soles of hands and feet.

The lesions often evolve from macules into red papules (hence, maculopapular)
What stage of syphilis is associated with its nickname as the "Great Imitator"?
Secondary Syphilis

The clinical manifestations and thus the Ddx of secondary syphilis are extensive = "The Great Imitator"
Describe latent syphilis.
Definition of latency: That stage of syphilis during which a specific treponemal antibody test is positive but during which there are no clinical manifestations of syphilis, including normal CSF findings.
- Latent disease = sub-clinical infection from which there can be relapses late in disease

• 90% of relapses occur during early latency (< 1 year).

• Relapses are less common during late latency (> 1 year) but transmission via blood transfusions and pregnancy may still occur.
How do you diagnose syphilis.
Clinically based on presentation and history

Serodiagnosis:
1) Non-treponemal serology = VDRL, RPR
• can be falsely-positive in some disease (eg lupus)
2) Treponemal serology = FTA-ABS, MHA-TP
• use treponemal antibodies
• used to confirm non-treponemal tests
What are the main types of complications associated with a tertiary/late syphilis infection?
1) Endarteritis obliterans (cardiovascular)

2) Neurosyphilis (meningovascular or parenchymatous)

3) Gumma (late benign syphilis)
What is a hallmark of tertiary/late syphilis complications?
blood vessel involvement
What is endarteriti obliterans?
Endarteritis obliterans:

the vasa vasorum of the aorta, causes medial necrosis with destruction of its elastic tissue --> aneursym of the ascending aorta --> to aortic regurgitation and coronary artery stenosis

Chronic inflammation of endarteritis obliterans causes fibroblastic proliferative thickening of arterioles found in all stages of syphilis.
What are the types of neurosyphilis?
1) Meningovascular
• vascular involvement
• hemiparesis, seizures, aphasia

2) Parenchyatous neurosyphilis
a. General paresis
• coritcal involvement
• personality changes, hyperactive reflexes, pupil accomodate but dont react
b. Tabes dorsalis
• spinal cord development
• shooting, lightning pain
• ataxia, trophic degenerative joint disease
What is gumma?
Gumma = Late Benign Syphilis

Destructive lesions most commonly found in the skeletal system, skin, and mucocutaneous tissues but can develop in any organ.

The cutaneous lesions range from superficial nodules to deep granulomatous lesions, which may break down to form punched-out ulcers.
Can T. pallidum cross the placenta?
Yes, and can cause Congenital syphilis:

1) Rhinitis
2) Frontal bossing
3) Saddle nose deformity
4) Hutchinson's teeth (widely spread, peg-shapped upper central incisors)
5) Keratitis (and blindness)
What is the treatment of syphilis?
Penicillin G

If allergic to penicillins, penicillin desensitization is recommended for pregnant patients. Doxycycline, ceftriaxone, and chloramphenicol may be used in other penicillin allergic patients.
How does HIV influence syphilis?
1) They enhance the acquisition and transmission of each other.

2) Syphilis in HIV-infected patients often follows a more protracted and malignant course, resulting in a high antigen load.

3) Co-infected patients often have extremely high titers on serologic tests for syphilis, and may fail to decrease in response to adequate treatment.

4) Relapses of syphilis after adequate therapy have been described in many HIV patients. For this reason, serologic follow-up is recommended. Patients who fail to have a serologic response should be retreated.
What are the nonvenereal treponematoses?
1) Yaws

2) Pinta

3) Bejel
What is the pathogen and pathogenesis of relapsing fever?
Borrelia hermsii (tick-borne) or Borrelia recurrentis (louse-borne) cause relapsing fever.

Borrelia can undergo antigenic mutations of its variable surface protein to alter its serology to evade host immune responses

Each changed serotype, causes a febrile relapse
Which ticks carry B. hermsii and B. burgdorferi?
Ornithodoros hermsi (soft body, rapid feeders) carry B. hermsii

Ixodes scapularis (hard body, slow feeders) carry B. burgdorferi
What disease does B. burgdorferi cause?
Lyme disease
What explains the current reemergence of Lyme disease?
During the 20th century, conditions improved for the ecology of Lyme disease.

Farmland revereted to woodland, deer proliferated, white-footed mice were plentiful.

Soil moisture and land cover were favorable for the Ixodes tick to thrive
Why is California a low risk area for Lyme disease?
Most Ixodes pacificus ticks are not infected with B. burgdorferi
What are the stages of Lyme disease?
1) Incubation (3-32 days)
2) Localized Infection (early infection - stage 1)
3) Disseminated Infection (early infection - stage 2)
4) Persistent Infection (late infection - stage 3)
Describe a localized infection of Lyme disease.
80% of patients have ERYTHEMA MIGRANS = slowly expanding skin lesions at the site of the tick bite.

As they expand, most lesions continue to have bright red outer borders and partial central clearing, appearing targetoid.

The skin lesion is often accompanied by influenza-like symptoms, such as malaise and fatigue, head-ache, arthralgias, myalgias, and fever.
Describe a disseminated infection of Lyme disease.
Within several days after the onset of the initial EM skin lesion, patients may develop multiple annular secondary lesions.

About 15% of untreated patients develop neurologic abnormalities.

The usual pattern consists of fluctuating symptoms of meningitis with superimposed cranial (particularly facial palsy = BELL's PALSY) or peripheral radiculoneuropathy
How do you Dx Lyme disease?
Local early infection: erythema migrans (targetoid) and tick exposure = clinical Dx bc serological tests often negative in first 1-2 wks

Disseminated early infection: almost all pts now have positive IgG response to B.burgdorferi (ELISA)
How do you Tx Lyme disease?
Oral Regimen
1) Doxycycline (100-mg bid)
2) Amoxicillin (500-mg tid)

Parenteral Regimen
3) Ceftriaxone (2-gm qd)

*10-13% of patients report persistent subjective symptoms and a failure to return to their pre-Lyme disease health status
Describe the Lyme disease vaccine.
1) B. burgdorferi expresses outer surface protein A (Osp A) while in the tick midgut

2) Moving to the tick saliva and into mouse blood, B. burgdorferi changes expression to Osp C

3) Immunization to Osp A: tick takes blood meal containing antibodies to Osp A and B. burgdorferi is killed in the tick midgut before switching to Osp C

4) Human studies were safe but vaccine was recently withdrawn due to concerns about induction of autoimmune arthritis
How do you prevent Lyme disease?
1) Tick Checks! Since 24-72 hours of tick attachment is necessary before transmission occurs, removal of the tick within 24 hours is sufficient to prevent Lyme disease.

2) Prophylactic doxycycline 200mg if an engorged nymphal tick is found.

3) Personal protective measures including protective clothing and tick repellents.

4) Annual treatment of yards with pesticides.

5) Landscape modifications: clearing brush and leaf litter.

6) Treatment of rodents and deer with acaricides.
Which two spirochetes exist in animal reservoirs?
1) Borrelias

2) Leptospiras
• can exist in mammals as well as be free-living

* T. pallidum only exists in human hosts
How does osmolarity influence the pathogenesis of leptospiras?
1) Renal colonization and urinary shedding in reservoir hosts animals (rodents, other small mammals)

2) Can survive outside the host in low osmolality conditions

3) Accidental infection of a new host whos physiological osmolarity induces adhesin expression allowing invasion, dissemination, multiplication, and a host inflammatory response
What disease do leptospiras cause?
1) Anicteric Leptospirosis

2) Icteric Leptospirosis
Explain anicteric leptospirosis.
Less severe form
- normal liver function

1) Incubation (5-14 days)
2) Septicemic Stage (3-7 days)
- Fever, myalgia, headache, abdom pain, nausea, vomiting, conjunctival suffusion
* bacteria can be found in blood and CSF
3) Agglutinating antibodies clear bacteria by delivering endotoxins to phagocytes
4) Immune Stage (0 days - 1 mo)
- Mild fever, headache, vomiting, aseptic meningitis
* bacteria can be found transiently in the urine during this stage
Explain icteric leptospirosis.
More severe form
- involves the liver
- life-threatening

1) Incubation (5-14 days)
2) Septicemic Stage (3-7 days)
- Fever, myalgia, headache, abdom pain, nausea, vomiting, conjunctival suffusion
* bacteria can be found in blood and CSF
3) Agglutinating antibodies clear bacteria by delivering endotoxins to phagocytes
4) Immune Stage (0 days - 1 mo)
- If there are sufficient bacteria present in the blood, the Ab delivery of endotoxin to phagocytes but causing jaundice, renal failure, hypotension, hemorrhagic pneumonitis
* bacteria can not be found in the urine
What are some risk factors for leptospirosis?
1) exposed mucous membranes or skin abrasions

2) time and degree of immersion in contaminated water

3) swallowing water

4) heavy rainfall or flooding
How do Dx leptospirosis?
The diagnosis of acute leptospirosis remains clinical, since serologic tests are usually negative at the time of clinical presentation.

1) Suspect leptospirosis in patients with an acute febrile illness after recreational exposure to natural bodies of fresh water.

2) Acute and convalescent serology should be sent - a four-fold rise in titer is diagnostic.

3) Direct detection by culture or PCR.

4) The gold standard serologic test is the MAT (microscopic agglutination test), which is available only in reference centers. An IHA (indirect hemagglution test) and IgM ELISA are more widely available.
How do you Tx leptospirosis?
Treatment of severe leptospirosis (patients requiring hospitalization): Ampicillin (0.5 - 1 gm IV q6h).

Treatment of mild leptospirosis (outpatients): oral doxycycline 100 mg po bid.
How do you prevent leptospirosis?
1) Travelers should be taught to minimize exposure to potentially contaminated water.

2) Protective clothing, especially footwear, and other measures to prevent dermal cuts and abrasions are important.

3) Travelers to the tropics should avoid submersion in, and drinking from, surface water.

4) Chemoprophylaxis with doxycycline 200 mg once weekly was found to be effective. Doxycycline may cause GI upset and photosensitivity, and is contraindicated during pregnancy and with children.
Some travel medicine specialists recommend azithromycin instead.
What are some general similarities and differences between spirochetes?
Similarities = infections caused by invasive spirochetes are characterized by widespread dissemination (including the central nervous system) and the ability to persist in the host for long periods of time

Differences =
• T. pallidum has direct transmission and a single host, humans
• B. burgdorferi has tick-borne transmission and uses ticks and humans for hosts
• L. interrogan has indirect transmission and can be free-living or use humans and small mammals as hosts
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