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What is the recommended treatment for late latent syphilis in a patient without a penicillin allergy?
What is the recommended treatment for late latent syphilis in a patient without a penicillin allergy?
Which of the following is a characteristic symptom of a Jarisch-Herxheimer reaction?
Which of the following is a characteristic symptom of a Jarisch-Herxheimer reaction?
What is the typical recurrence rate of genital herpes infections within the first year?
What is the typical recurrence rate of genital herpes infections within the first year?
Which population has the highest seropositivity for HSV-2?
Which population has the highest seropositivity for HSV-2?
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In what scenario does the risk of HSV-2 transmission significantly decrease?
In what scenario does the risk of HSV-2 transmission significantly decrease?
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What is the causative agent of syphilis?
What is the causative agent of syphilis?
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Which of the following was a treatment for syphilis before modern medicine?
Which of the following was a treatment for syphilis before modern medicine?
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What phase of syphilis is characterized by symptoms that can include skin lesions and flu-like signs?
What phase of syphilis is characterized by symptoms that can include skin lesions and flu-like signs?
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Which neurological condition is indicated by the symptoms described in the poem?
Which neurological condition is indicated by the symptoms described in the poem?
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What is the average prevalence of syphilis in the United States during the 1930s?
What is the average prevalence of syphilis in the United States during the 1930s?
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Which of the following stages of syphilis occurs after the initial infection and before the secondary stage?
Which of the following stages of syphilis occurs after the initial infection and before the secondary stage?
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What societal impact did untreated syphilis have in the early 20th century?
What societal impact did untreated syphilis have in the early 20th century?
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What type of data is represented in the syphilis rates mentioned for various years and demographics?
What type of data is represented in the syphilis rates mentioned for various years and demographics?
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What is the average duration of painful vesicles in a primary HSV infection?
What is the average duration of painful vesicles in a primary HSV infection?
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Which of the following is the most sensitive method for diagnosing HSV?
Which of the following is the most sensitive method for diagnosing HSV?
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What treatment regimen is recommended for recurrent HSV infections?
What treatment regimen is recommended for recurrent HSV infections?
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What clinical presentation is characteristic of Granuloma Inguinale?
What clinical presentation is characteristic of Granuloma Inguinale?
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For which condition is the etiology Klebsiella granulomatis?
For which condition is the etiology Klebsiella granulomatis?
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What is a common symptom during the prodromal phase of a recurrent HSV infection?
What is a common symptom during the prodromal phase of a recurrent HSV infection?
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What is the recommended treatment for Granuloma Inguinale?
What is the recommended treatment for Granuloma Inguinale?
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What is the significance of viral shedding in HSV-1 infections?
What is the significance of viral shedding in HSV-1 infections?
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What virus is primarily responsible for genital warts?
What virus is primarily responsible for genital warts?
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Which types of HPV are most commonly associated with cervical cancer?
Which types of HPV are most commonly associated with cervical cancer?
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What is the recommended age range for HPV vaccination?
What is the recommended age range for HPV vaccination?
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Which treatment option is not typically used for genital warts?
Which treatment option is not typically used for genital warts?
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What screening is recommended for sexually active women under the age of 25?
What screening is recommended for sexually active women under the age of 25?
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What is the primary mode of transmission for syphilis during its infectious stages?
What is the primary mode of transmission for syphilis during its infectious stages?
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Which group has shown the highest percentage increase in syphilis cases in Nebraska since 2017?
Which group has shown the highest percentage increase in syphilis cases in Nebraska since 2017?
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What clinical finding is associated with primary syphilis?
What clinical finding is associated with primary syphilis?
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What percentage of cases of secondary syphilis may exhibit CNS symptoms?
What percentage of cases of secondary syphilis may exhibit CNS symptoms?
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Which of the following is a characteristic of tertiary syphilis?
Which of the following is a characteristic of tertiary syphilis?
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What is an indicator that a person has latent syphilis?
What is an indicator that a person has latent syphilis?
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What is the average time from infection to the development of a primary chancre?
What is the average time from infection to the development of a primary chancre?
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What condition can develop due to vigorous progression of untreated secondary syphilis?
What condition can develop due to vigorous progression of untreated secondary syphilis?
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What common cardiovascular manifestation is associated with tertiary syphilis?
What common cardiovascular manifestation is associated with tertiary syphilis?
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What percentage of cases of syphilis is co-infected with HIV?
What percentage of cases of syphilis is co-infected with HIV?
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Study Notes
Syphilis
- Syphilis is caused by the spirochete Treponema pallidum, which can’t be cultured.
- Before effective treatment, syphilis was a leading cause of cardiovascular and neurologic disease.
- The prevalence of syphilis was 8-14% in the 1930s.
- Syphilis has multiple phases, including incubation, primary, secondary, early latent, late latent, and late tertiary stages.
Syphilis Epidemiology
- Syphilis rates continue to climb, driven by an increase in cases among men who have sex with men (MSM) and women.
- Risk groups for syphilis include MSM, people with HIV (up to 50% of cases are co-infected), and minorities, especially American Indian and African American males.
- The highest rates of syphilis infection are found in urban areas of the United States, and especially in the south.
- Syphilis is spread through contact with infectious lesions during the primary and secondary stages.
- Syphilis is not sexually spread after four years since infection.
- Congenital syphilis is usually acquired in utero and affects the infant.
- Increasing rates of congenital syphilis are considered sentinel events.
Pathogenesis
- Syphilis spreads through mucous membranes or abraded skin.
- The organism disseminates throughout the body, with an incubation period of 3-90 days but typically around 3 weeks.
- Primary syphilis: Primary syphilis is characterized by the development of a chancre at the site of inoculation.
- Secondary syphilis: Secondary syphilis occurs 2–8 weeks after primary syphilis (25% of individuals). It is characterized by a rash, constitutional symptoms, such as fever and malaise, and other signs.
- Latent syphilis: Latent syphilis is asymptomatic but serologic evidence of infection is present. Early latent syphilis is defined as one year or less since infection, while late latent syphilis is defined as more than one year since infection.
- Late or tertiary syphilis: Late or tertiary syphilis develops in 25–40% of individuals, typically 1–30 years after infection. Late syphilis involves the cardiovascular system, gummas, and central nervous system.
Pathological Findings
- Obliterative endarteritis, characterized by concentric endothelial and fibroblastic proliferative thickening, is a key pathological feature of syphilis.
- Lesions in the vasa vasorum of the cardiovascular and central nervous systems are responsible for the disease manifestations.
Clinical Presentation: Primary Syphilis
- Primary chancre: The primary chancre is a painless ulcer, typically on the genitals, anus, or mouth. It is typically a papule that evolves into an ulcer with an indurated, smooth base and raised cartilaginous borders. It resolves within 3-6 weeks without scarring.
- Painless regional lymphadenopathy: This is often observed with primary syphilis.
- The chancre can be present when secondary syphilis develops.
Clinical Presentation: Secondary Syphilis
- Dissemination and multiplication: Secondary syphilis is characterized by widespread dissemination and multiplication of T. pallidum.
- Constitutional symptoms: Fever, malaise, and generalized lymphadenopathy are common constitutional symptoms associated with secondary syphilis.
- Skin: Skin manifestations include a widespread maculopapular rash, often involving palms and soles, patchy alopecia (hair loss), condylomata lata (painless, moist, gray-white plaques in intertriginous areas), and mucous patches (painless silver-gray oral lesions).
- CNS: Central nervous system involvement (CNS) is present in 40% of individuals with secondary syphilis and can present as headaches, meningismus, cerebrospinal fluid abnormalities, aseptic meningitis, and cranial nerve abnormalities.
- Other: Other manifestations of secondary syphilis include glomerulonephritis, hepatitis, arthritis, uveitis, and otic conditions.
- Increasing incidence of ophthalmic syphilis is a concern.
Clinical Presentation: Tertiary Syphilis
- Cardiovascular: Cardiovascular involvement includes aneurysms, especially of the aorta, due to inflammation of the vasa vasorum.
- Gummas: Gummas are rare granulomatous tumor-like, destructive lesions affecting skin, bone, and other sites.
- CNS disease: Central nervous system disease can manifest at any stage of syphilis; secondary syphilis is the most common stage for neurosyphilis.
- Acute neurosyphilis: Often asymptomatic, this often occurs as a manifestation of secondary syphilis.
- Late neurosyphilis: Can occur several years after infection. This presents as:
- Meningovascular syphilis: Multiple small infarcts due to vascular occlusion.
- These infarcts can result in symptoms such as stroke, dementia, and seizures.
- Parenchymatous syphilis:
- General paresis: A late manifestation of neurosyphilis, this involves the brain and leads to psychiatric and neurological complications. It usually presents 15–20 years post-infection.
- Symptoms include emotional lability, dementia, personality changes, speech disturbances, seizures, and Argyll Robertson pupils (pupils that accommodate but do not react to light).
- Tabes dorsalis: This involves degeneration of the posterior columns and dorsal roots of the spinal cord. - Symptoms: Ataxia, paresthesias, shooting pain ("lightning pains"), bowel and bladder difficulties, decreased reflexes, and a positive Romberg test. - Associated symptoms include Charcot joints (due to denervation) and foot ulcers.
- General paresis: A late manifestation of neurosyphilis, this involves the brain and leads to psychiatric and neurological complications. It usually presents 15–20 years post-infection.
- Meningovascular syphilis: Multiple small infarcts due to vascular occlusion.
Latent Syphilis
- Latent syphilis: This is asymptomatic syphilis with positive serology, but no evidence of disease.
- Early latent syphilis: A diagnosis defined as less than one year since infection, or in the absence of a known duration.
- In pregnancy, it is important to consider desensitizing the patient for penicillin treatment, though not always recommended for early latent syphilis.
- Late latent syphilis: This is defined as more than one year since infection, or in the absence of a known duration, and is not neurosyphilis.
Treatment
- Penicillin G: Benzathine penicillin G is the treatment of choice for syphilis. It is administered intramuscularly once per week for three administrations.
- For late latent syphilis, a single dose of 2.4 million units is given.
- For neurosyphilis, penicillin G is administered intravenously every 4 hours for 10–14 days.
- Jarisch-Herxheimer reaction: This is a common adverse reaction to penicillin therapy for syphilis. It is characterized by fever, chills, myalgia, headache, flushing, and decreased blood pressure.
- The reaction typically lasts 12–24 hours.
- Follow-up: RPR or VDRL tests should be performed at 6, 12, and 24 months after treatment to monitor for a four-fold decrease in titers within one year.
- Sexual partners: All sexual partners within the last 90 days should be treated for syphilis.
- HIV: It is crucial to screen all patients with syphilis for HIV.
Genital Herpes
- Etiology: The most common causative agent for genital herpes is Herpes Simplex Virus type 2 (HSV-2), responsible for 70-95% of cases. Herpes Simplex Virus type 1 (HSV-1) can also cause genital herpes.
- Epidemiology: At least 50 million people in the US are infected with genital herpes.
- Incidence: True incidence is unknown, as many cases are asymptomatic.
- HSV-2 seropositivity: Rates vary widely, depending on the location, sexual risk factors, and gender.
- Prevalence among men: 18%
- Prevalence among women: 26%
- Prevalence in STD clinics: 31–64%
- Prevalence in Africa: 41–74%
- Risk factors: Risk factors for genital herpes include being female, having multiple sexual partners, and being Black.
- HSV-1: Prior HSV-1 infection does not protect against transmission of HSV-2, but it can increase asymptomatic infection by threefold.
HSV Pathogenesis
- Reactivation: Most people with HSV infection experience reactivation, with 90% experiencing recurrences within one year.
- The median number of recurrences per year is 4-5, with the frequency decreasing over time.
- HSV-2 tends to reactivate more frequently than HSV-1.
- Immunocompromised individuals, particularly those with impaired cell-mediated immunity due to HIV or immunosuppressive therapy, are at risk for more frequent and severe reactivation.
HSV Transmission and Shedding
- Transmission: Both symptomatic and asymptomatic individuals can transmit HSV.
- In discordant couples (one partner infected with HSV-2), transmission rates range from 3% to 12% per year, with the median time to transmission around 3 months.
- Transmission is reduced by 50% if the partner is aware of the HSV-2 status.
- Increasing HSV-1 genital infection: The incidence of HSV-1 genital infection is rising, potentially due to changing sex practices and declines in HSV-1 seroprevalence, suggesting a shift toward oral-genital transmission.
- Frequent viral shedding: Viral shedding occurs frequently, often without symptoms. About 1 in 4 days (2–75% estimated) show viral shedding, with sufficient viral levels to transmit HSV.
HSV Clinical Presentation
- Primary infection: Incubation period is typically 2–12 days (average of 4 days). It usually presents with more severe symptoms and a longer duration compared to non-primary infection.
- Symptoms: Fever, headache, malaise, local pain/itching, dysuria, tender inguinal lymphadenopathy.
- Lesions: Painful vesicles, ulcers, and pustules (avg. duration: 19 days)
- Non-primary infection: Symptoms tend to be less severe than with primary infection.
- Recurrent infection: Symptoms are less severe than primary infection but can be preceded by a prodrome of tingling or shooting pains.
- Lesion duration: 10 days.
- Other forms of HSV infection: Herpes virus can also cause proctitis, aseptic meningitis, Whitlow (infection of the fingers), and ocular herpes.
HSV: Diagnosis
- Tzanck prep: Scraped material is smeared onto a slide to look for multinucleated giant cells and intranuclear inclusions.
- Culture: Cells are grown in a laboratory to look for cytopathic effect (CPE), a characteristic damage to the cells caused by the virus.
- Polymerase Chain Reaction (PCR): This is the most sensitive method for detecting HSV.
- Serology: Serological tests, which detect antibodies to HSV, are less commonly used.
- Direct Fluorescent Antibody (DFA): This technique uses fluorescein-labeled HSV-1/HSV-2 antibodies to detect the virus.
HSV: Treatment
- Primary infection: Treatment for primary infection is always recommended to decrease duration and severity of symptoms.
- Acyclovir, valacyclovir, or famciclovir are usually prescribed for 7–10 days.
- Recurrent infection: Treatment should be initiated as soon as possible.
- Acyclovir 800mg TID for 2 days, famciclovir 1g BID for 1 day, or valacyclovir 500mg BID for 3 days can be used for this purpose.
- Suppressive therapy: This is recommended for individuals who have 6 or more recurrences per year or who are experiencing severe distress or disease.
- Suppressive therapy decreases the risk of transmission by 50%.
- Acyclovir 400mg BID, famciclovir 250mg BID, or valacyclovir 500mg daily (1g daily if more than 9 recurrences per year) is commonly used for this purpose.
Granuloma Inguinale (Donovanosis)
- Etiology: Klebsiella granulomatis is the causative agent.
- Previously referred to as Donovania and Calymmatobaterium.
- It is a gram-negative bacterium with bipolar staining, giving rise to characteristic Donovan bodies.
- Epidemiology: Common in India, New Guinea, the Caribbean, and Brazil.
- Presentation: Incubation period ranges from 8 to 80 days.
- Usually begins as a nodule, evolving into a painless ulcer.
- The ulcers are characterized by being beefy, granulomatous, with rolled edges, and prone to bleeding easily.
- Diagnosis: Smears and crush preparations are useful to identify Donovan bodies.
- Treatment: Continuous therapy until healing occurs.
- Tetracycline or doxycycline are commonly used.
- Azithromycin 1g weekly may also be effective.
Chancroid
- Etiology: Haemophilus ducreyi is the causative agent.
- Epidemiology: Though formerly prevalent in the US, it is currently rare and often underdiagnosed.
- Common in sub-Saharan Africa, Southeast Asia, and Latin America.
- Highly infectious.
- Presentation: Incubation period is typically 4 to 10 days, but can range from a few days to weeks.
- Initially, a papule develops that quickly evolves into a painful ulcer with a ragged, undermined, and friable base.
- The ulcers tend to be multiple and often coalesce.
- Associated with painful, suppurative, and enlarged regional lymph nodes.
- Diagnosis: A combination of clinical presentation, gram stain, and culture can help confirm the diagnosis.
- Treatment: Effective treatments include single-dose ceftriaxone or azithromycin, or a 7-day course of oral ciprofloxacin or erythromycin.
Genital Warts/Condyloma Acuminata
- Etiology: Human Papillomavirus (HPV) is the causative agent.
- Epidemiology: The lifetime risk of genital HPV infection for sexually active individuals is at least 50%.
- Certain HPV types are associated with cervical cancer (16, 18, 31, 33, 35, 45).
- Other types are associated with genital warts (6, 11).
- Presentation: Usually presents as flesh-colored or gray, hyperkeratotic, exophytic papules, or as flat, velvety lesions.
- May appear as cauliflower-like growths, single lesions, or clusters.
- Diagnosis: Diagnosis is primarily clinical.
- Acetic acid application can help visualize the lesions more readily.
- Treatment: Various treatment options are available, including chemical, immunological, and surgical approaches.
- Chemical treatments: Podophyllin, trichloroacetic acid, 5-fluorouracil (5-FU)
- Immunological treatment: Imiquimod
- Surgical treatment: Cryotherapy, laser ablation, excision
HPV Prevention
- Vaccination: Effective HPV vaccines are available.
- Cervarix: Targets HPV types 16 and 18.
- Gardasil: Targets HPV types 6, 11, 16, and 18.
- Gardasil 9: Targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
- Vaccines are highly effective against the targeted HPV types (up to 100% effective) and can prevent cervical cancer precursors with greater than 90% efficacy.
- Most effective when administered before HPV acquisition.
- Vaccination is recommended even for individuals with cervical abnormalities or warts.
- Typically given as three intramuscular injections: 0, 1–2 months, and 6 months.
- Individuals aged 9–14 can complete the vaccination with two injections, given 0 and 6–12 months.
- Individuals aged 15–26 and immunocompromised individuals need three injections.
- Recommendations:
- All adolescents at age 11–12 should be vaccinated.
- Vaccination is recommended for individuals aged 13–26 who have not previously been vaccinated.
- Vaccination may be safe for individuals aged 27–45, but the benefits are minimal compared to younger ages.
CDC Screening Recommendations
- HIV, syphilis, gonorrhea, chlamydia: All individuals aged 13–64 years should be tested for HIV at least once.
- Men who have sex with men (MSM) should be screened yearly.
- They should also be tested for syphilis, gonorrhea, and chlamydia more frequently (every 3–6 months) if they have multiple or anonymous partners or are on pre-exposure prophylaxis (PrEP).
- Men who have sex with men (MSM) should be screened yearly.
- Sexually active men: Men who are highly at risk for sexually transmitted infections, such as MSM, individuals attending STD clinics, and those in correctional facilities, should be screened for gonorrhea and chlamydia and also for HIV.
- Pregnancy:
- Screening for HIV, hepatitis B, syphilis, chlamydia, gonorrhea, and hepatitis C (if at increased risk) is recommended during pregnancy.
- Testing for bacterial vaginosis, trichomoniasis, and herpes simplex virus is not typically recommended during pregnancy.
- Sexually active women: Sexually active women should be screened for chlamydia and gonorrhea, especially those with a history of sexually transmitted infections, multiple sexual partners, or sex with partners at risk of sexually transmitted infections.
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