MICRO - Genital Ulcer Diseases
How are STDs/STIs organized clinically?
Genital Ulcer Diseases (GUD) Urethritis-cervicitis: Genital warts - HPV
What is the cause of Genital Warts?
Human papilloma virus
Prophylaxis/Prevention of Chancroid
Latex condoms only reduce the risk of chancroid, it does not eliminate it.
Immunosuppressed patients who acquire syphilis are prone to...
develop a more severe pyphilic disease
T. pallidum-specific Antibodies: IgG titer peak ...
during the end of secondary syphilis, after the IgM peak, but declines very slow over time.
What can be the outcome of Tertiary stage of LGV?
genital ulcers, fistulas and rectal strictures (a chronic inflammatory response) Genital elephantiasis
Describe condymomata lata of secondary syphilis
highly infectious, raised, painless, with a central erosion and covered with a thin membrane and are found on the genital, oral, and/or rectal mucosa (warm moist tissue).
How long can the latent stage of syphilis persist?
months to years, average duration is 4 years.
What is Treponema pallidum doing during "Incubation & Primary Syphilis" ?
multiplying locally and later enters and disseminates via the draining lymphatics and/or bloodstream
Characteristics of Haemophilus ducreyi
pleomorphic gram-negative rod highly fastidious
how is Asymptomatic neurosyphilis diagnosed?
positive CSF serology (reactive VDRL), increases in WBC cells present and increased total protein.
The term ________ is given for the manifestations of secondary syphilis.
protean (from the greek - assuming different forms)
T. pallidum-specific Antibodies: IgM titer peak during....
secondary syphilis and then rapidly decline
Discuss Treatment Follow-up for Syphilis
serology (RPR) at 3, 6, 12, 24 months post treatment. Expect declining antibody titers over 1 to 2 year period.
Latent syphilis is arbitrarily divided into early- and late-latent syphilis based on ....
the ability to relapse into secondary disease.
If secondary syphilis is not properly treated or goes without treatment, a patient will enter....
the latent phase!
What enables the macrophages to kill intracellular chlamydia?
Th1 cell-derived cytokine, gamma-IFN
_____________ is a disseminated infection involving virtually every organ system and occurs about 6 weeks after exposure and lasts for 1 or 2 months if untreated.
Secondary syphilis
How are Soft Chancre different from Hard Chancre?
Soft Chancre lesions have the presence of pain, larger size, and ragged appearance. (Soft on left, Hard on right)
One or more painful/tender, non-indurated papules form, become pustules (with a purulent exudate), erode, and ulcerate with ragged edges. They can often spread and coalesce.
Soft Chancre of Chanroid
What is agent that causes of Lymphogranuloma venereum (LGV)?
Specific Serotypes of Chlamydia Trachomatis such as L1, L2, & L3.
For ALL LESIONS in and around genitalia, rectum, lips, or hands of sexually active persons - test for?
Syphilis Herpes Chancroid
Syphilis is a ____________ disease involving the inflammatory response, which can result in pathology in various organs during stages of the full course of disease.
Systemic disease
AS with other chlamydial agents, ______________ is likely the key immune response.
T cell-mediated immunity
Which stage of syphilis? A slow, progressive, inflammatory degenerative disease affecting any organ system and is refractory to antibiotic therapy and is universally fatal?
Tertiary/ Late Stage
____ response appears to dominate in primary syphilis, the agent drives a conversion to ___ response in secondary syphilis.
Th1 = primary syphilis Th2 = secondary syphilis
What is the manifestations that is almost pathopneumonic for LGV and how is it created
The groove sign - during the 2nd stage when extensive inguinal lymphadenopathy with bubo formation is bisected by Poupart's ligament!
True/False: Treponema pallidum's Sensitivity to various environmental factors is great.
True (sensitive to high/low temp, desiccations, soap, etc)
What is syphilis considered a disease of 3rds? One-third of all persons with Secondary syphilis....
1) are spontaneously cured 2) remain latently infected for life 3) progress to tertiary or late syphilis that is fatal
When does the tertiary stage of syphilis occur?
10 years post exposure
How long does the Hard Chancre last?
2 to 6 weeks
secondary syphilis manifestations that results in patchy hair-loss with a "moth-eaten" appearance of scalp & eyebrows.
Alopecia
What can prevent the Tertiary Stage of LGV from every occurring?
Antibiotics!
Treatment for Chlamydia trachomatis.
Azithromycin Doxycycline
Treatment for Chancroid
Azithromycin Erythromycin Ceftriaxone
How do you diagnose Chancroid?
Clinical Signs Gram-stain (pictured - school of fish) Culture (chocolate agar)
How is LGV diagnosed?
Clinical Signs and Symptoms Serology Isolation of organism from tissue/pus EIA PCR/LCR
Neurosyphils is broken into the early and late neurosyphilis. What are the 3 forms of early neurosyphilis?
- Asymptomatic - Symptomatic syphilitic meningitis - Menigovascular
Neurosyphils is broken into the early and late neurosyphilis. What are the 2 forms of late neuropsyphilis?
- General paresis - Tabes dorsalis
List the stages of Syphilis
- Incubation period (avg 3 weeks) - Primary syphilis. - Initial latent period. - Secondary syphilis. - Latent syphilis: (Early and late latent) - Tertiary or late syphilis (Neurosyphilis, Cardiovascular syphilis, or Gumma)
What are the manifestations of late syphilis?
- Neurosyphilis - Cardiovascular syphilis - Gumma
Clinical Manifestations of Secondary Syphilis
- skin rash - mucous patches (condylomata lata) - alopecia - constitutional signs and symptoms - organ system (the great imitator)
What are the clinical manifestations of chancroid?
- soft chancre - inguinal buboes
Name the Sexually transmitted agents of cervicitis, urethritis, etc. and pelvic inflammatory disease (PID)
Bacterial: - Chlamydia trachomatis - Neisseria gonorrhoeae (other agents)
Name the Bacterial & Viral Agents that cause Genital Ulcer Disease.
Bacterial: - Syphilis - Chancroid - Lymphogranuloma venereum (LGV) - Granuloma inguinale Viral: - Herpes Simplex Virus
Name the spirochete that causes Lyme disease and relapsing fever.
Borrelia
The Soft Chancre may be accompanied 7 to 10 days later by ___________. Can become suppurative & even rupture spontaneously, draining to the outside.
Bubo
The type of inflammatory cells that migrate to the site of infection that are readily infected with HIV include...
CD4 T cells and monocytes
Ascending aorta most commonly involved. Vasculitis/Endarteritis obliterans of vasa vasorum blocks the vessels, especially those associated with the aortic arch leading to aortic stenosis, aortic regurgitation, coronary artery ostial stenosis, aortic aneurysm. Blocks the vessels that feed the aorta.
Cardiovascular Syphilis (Manifestation of Tertiary stage syphilis)
Mode of transmission for Treponema pallidum
Direct Contact (sex is primary) Transplacentally Lab workers accidentally Blood and Blood transfusions
What is the potential outcome for a patient to have a Jarisch-Herxheimer reaction during early stages of syphilis versus late stages of syphilis?
Early - more significant systemic response Late - CNS or Cardiovascular damage
When does "early latent" and "late latent" stages of syphilis take place?
Early latent - after secondary syphilis to end of first year of infection. Late latent - end of 1st year to end of 4th year (arbitarily).
___________ is proliferative concentric thickening of small blood vessels by endothelial & fibroblastic cells causing a reduction in the caliber of the vessel lumen & even blocking the vessels. Partially responsible for primary & secondary lesions & manifestations of tertiary syphilis.
Endarteritis/ Endarteritis obliterans
What is the vascular pathology of Syphilis?
Endarteritis/Endarteritis obliterans Periarteritis
What happens after LVG (L1, L2, L3) infect a tissue macrophages at the site of primary infection?
Enter the draining lymphatics and lymph nodes in the area and then find numerous other macrophages to infect and carry out their life cycle.
True/False: Hard chancres are easily found by the patients.
False - 60% of patients do not recall lesions because they are painless and can be very small or located anatomically to go unnoticed (mostly women).
True/False: Antibodies made in response to the infection prevent infection and cause resolution of the infection.
False - Antibodies are made in response to the infection and these may be used diagnostically, but do not prevent infection or cause resolution of infection.
True/False: a Hard single chancre of primary syphilis is extremely painful.
False - Hard Chancre are painless while Soft Chancres are painful!
True/False: Treponema pallidum's cells can be seen on gram stain.
False - Treponema pallidum's cells are too thin to be seen on gram stain. T. pallidum is visible on Dark microscopy (picture).
True/False: A person is only infectious during relapse to secondary syphilis occurring during first year of exposure.
False - a person is considered infectious during all relapses into secondary syphilis regardless of when they occur
True/False: Only the condylomata lata are highly infectious and not the skin rash.
False - all lesions are highly contagious
True/False: Condylomata lata are not highly infectious
False - condylomata lata are highly infectious
True/False Haemophillus ducreyi cannot be cultured just like T. pallidum.
False - highly fastidious but can be cultured in vitro under special conditions (usually on chocolate agar at a 34 to 35 degrees Celsius for 2 to 9d in 10% CO2.)
True/False: The Treponema pallidum transmission is by fomites
False - only person-to-person Bottom line, infection requires the kind of close-personal contact that normally only occurs when two people are having sex.
True/False: All stages of syphilis will have a positive serology.
False - only the latent phase will have a positive serology.
True/False: Treponema pallidum is easily cultured in vitro.
False - organisms has a low growth rate and cannot be cultured in vitro
True/False: Yaws, pinta, bejel, are STDs/STIs.
False - they are not STD/STI
What are the signs and symptoms of a Jarisch-Herxheimer Reaction?
Fever (above 100.4 F or 38.0 C) Chills/Rigor Malaise Headache Myalgia Tachycardia (above 100 bpm)
Morphologic characteristics of Treponema pallidum.
Gram negative Motile Spirochete
Chancroid (Soft chancre) is caused by...
Haemophilus ducreyi
During Primary Syphilis, a _____________ develops at the point of entry (spirochetes multiply locally), is a button-like induration (i.e., firm-hard), sharply demarcated, clean based, lesion with an eroded center and serous discharge, usually painless and is highly infectious.
Hard Single Chancre
The prevalence is high for LGV in...
Homosexual populations in the US Tropical & Subtropical areas
Natural habitat for Treponema pallidum
Humans are the sole host and reservoir
Endotoxic shock-like response (result of dead or dying treponemes in blood) that often occurs during treatment approximately 2 to 14 hours after treatment is initiated. Patients must be warned.
Jarish-Herxheimer Reaction
Name the Spirochete that causes leptospirosis
Leptospira
What are constitutional signs and symptoms?
Low-grade fever Malaise Headache Arthralgia Lymphadenopathy
Unlike the other LGV serovars, which infect epithelia cells almost exlusively, the L1, L2, & L3 serovars have an affinity for...
Macrophages
CNS damage results from cerebral vascular occlusion and infarction causing focal neurologic signs corresponding to the size and location of the lesion.
Meningovascular: obliterative endarteritis of meninges, brain, and spinal cord.
Treatment for Jarisch-Herxheimer Reaction for Syphilis.
NSAIDS Prednisone (for severe JH rxn)
Is there systemic immune response during the primary disease of chancroid (ulcerative stage before further lymph node involvement)?
No - Unlike T. pallidum, there is no systemic immune response, thus it is likely that the infection remains confined to the ulcer area until further invasion of the lymphatics occur.
What are the clinical signs of the latent phase?
None - the patient is asymptomatic (hence the name "latent syphilis")
Describe the Inguinal Syndrome/Second Stage
Occurs 2 to 6 weeks following exposure and results in extensive inguinal lymphadenopathy with bubo formation and my bisect the inguinal mass by Poupart's Ligament producing a "groove sign" for LGV. Patient may have Fever an other symptoms.
Nonpathogenic Treponema are normal flora of humans and are present where?
Oral cavity All mucosal surfaces (Diagnosis of syphilis requires differentitating between the Treponema NF vs T. pallidum)
What often will accompany a hard chancre 7 to 10 days after the chancre develops?
Painless, regional (blateral inguinal) and generalized lymphadenopathy
____________ is the proliferation of the adventitial cells (pericytes) and cuffing of the vessel by inflammatory cells consisting of monocytes, plasma cells, and lymphocytes.
Periarteritis
Discuss the cell wall architecture of the Treponema pallidum.
Phospholipid outer membrane - low proteins - no LPS Lipoproteins ( important J-H rxn)
What stage of LVG is 3 to 30 days following infection, a lesion forms. This may or may not be present or recognized by the patient. It is a small inconspicuous genital papule or herpetiform ulcer of short duration and few symptoms.
Primary Lesions
What are the stages of LGV?
Primary Lesions Inguinal (Second stage) Syndrome Tertiary Stage ( Chronic Inflammatory response)
When dos latent syphilis end?
Therapeutic cure occurs or tertiary manifestations develops
Treatment for Congenital Syphilis (CS)
Treat gravid female with benzathine penicillin for more than 1 month prior to birth.
Name the Spirochete that causes syphilis, yaws, bejel, pinta, and part of the NF on mucosal surfaces.
Treponema
Numan pathogenic Treponema that causes syphilis (hard chancre), a genital ulcer.
Treponema pallidum
True/False: Both IgM & IgG T. pallidum-specific antibodies are present when the clinical signs appear.
True
True/False: Chancroid is the STD most strongly associated with increase risk of HIV transmission.
True
True/False: During the latent phase, the patient is not infectious but the blood is.
True
True/False: Each time a patient manifests with signs and symptoms of secondary syphilis, the patient is infectious to his/her partners.
True
True/False: Syphilis should be included in the differential diagnosis of any lesion or ulcer of the genitalia, rectum, anus, lip or hand of sexually active patients.
True - because secondary bacterial or viral infections of the chancre can alter its appearance
Why is syphilis called "the great imitator"?
Virtually any organ system can become involved, but commonly the liver (hepatitis); kidney (immune-complex glomerulonephritis); eye, CNS (meningitis/encephalitis), arthritis, GI tract.
When can an initial latent period of syphilis occur?
after resolution of the primary chancre and before the patient progresses to secondary syphilis
Describe the skin rash of secondary syphilis
bilaterally symmetrical, non-pruritic, infectious skin rash that usually starts on the palms of the hands and the soles of the feet, the mouth, anus and spreads throughout the body. Can be macular, maculopapular, pustular, etc.
