Key points
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Sexually transmitted infections (STIs) continue to be a significant cause of morbidity and public health risk.
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Since 2011 the incidence of primary and secondary syphilis is increasing, particularly in men who have sex with men (MSM).
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Gonorrhea and chlamydia remain the main causes of bacterial urethritis and cervicitis.
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Human papillomavirus (HPV) can cause benign and malignant lesions and remains difficult to treat but can be prevented with vaccination.
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Primary prevention, behavior modification counseling, partner notification, and early treatment continue to be the mainstays in preventing the spread of STIs.
Introduction
STIs encompass a group of infections that can be spread or acquired through sexual contact. The Centers for Disease Control and Prevention (CDC) estimates approximately 20 million new STIs per year in the United States at a cost of approximately $16 billion. Half of these infections are in people between the ages of 15 and 24 years old. Each infection has the potential to pose significant immediate and long-term harm, affecting health and well-being. Primary prevention of STIs, through safe sex practices and partner awareness, can help decrease the incidence of many STIs. By far the most important tool to assist in the control of STIs is early diagnosis and treatment of these infected. This is evident in the decreased incidence in syphilis and gonorrhea seen from the 1980s to the early 2000s. The most recent surveillance updates by the CDC have identified an overall decrease in the rates of Chlamydia and gonorrhea in the general population. In 2013 there were 1,401,906 cases of Chlamydia trachomatis infection in the United States, representing an infection rate of 446.6 cases per 100,000 population. This represented a decrease of 1.5% compared with the rate in 2012. In women, gonorrhea infection has also decreased by 5%; however, an increase of 4% was seen in men. In 2010 the rates of primary and secondary syphilis experienced their first decline in 10 years; however, from 2011 to 2013 the rates have increased by more than 20%.
Individuals at the highest risk for contracting an STI are sexually active young adults between the ages of 18 and 25. Other important risk factors are the number of sexual partners, new sex partners, use of illicit drugs, admission to a correctional facility, and a prior history of STI. A newly described risk factor for STI is the use of erectile dysfunction medications in older men. A review of men prescribed ED medication found a 2- to 3-fold increase in the rate of STIs in men taking erectile dysfunction medications compared with men not taking these medications. Recent travel is also an important risk factor for the acquisition of STIs and has been seen in approximately 2.9% of illnesses in returning travelers.
Primary prevention of STIs begins with recognizing the risk behaviors of individual patients and counseling on changing these behaviors to prevent the acquisition of STIs. The US Preventive Services Task Force (USPSTF) recommends high-intensity behavioral counseling for all sexually active adolescents and adults. This involves routinely obtaining a sexual history on all patients and a discussion of behavior modifications and changes to at-risk practices. These counseling interventions have demonstrated efficacy in reducing acquisition rates of syphilis, Chlamydia, gonorrhea, and trichomoniasis. The CDC also promotes obtaining a sexual history focusing on the 5Ps: Partner(s), Prevention of pregnancy, Protection form STIs, sexual Practices, and Past history of STIs. These questions can lead to conversations about primary and secondary prevention. Prevention counseling should be provided in a safe, nonjudgmental, and empathetic environment.
This review focuses on the common causes of STIs. The focus is on the causes of ulcerative and nonulcerative diseases, condyloma, and a discussion on partner notification and treatment.
Introduction
STIs encompass a group of infections that can be spread or acquired through sexual contact. The Centers for Disease Control and Prevention (CDC) estimates approximately 20 million new STIs per year in the United States at a cost of approximately $16 billion. Half of these infections are in people between the ages of 15 and 24 years old. Each infection has the potential to pose significant immediate and long-term harm, affecting health and well-being. Primary prevention of STIs, through safe sex practices and partner awareness, can help decrease the incidence of many STIs. By far the most important tool to assist in the control of STIs is early diagnosis and treatment of these infected. This is evident in the decreased incidence in syphilis and gonorrhea seen from the 1980s to the early 2000s. The most recent surveillance updates by the CDC have identified an overall decrease in the rates of Chlamydia and gonorrhea in the general population. In 2013 there were 1,401,906 cases of Chlamydia trachomatis infection in the United States, representing an infection rate of 446.6 cases per 100,000 population. This represented a decrease of 1.5% compared with the rate in 2012. In women, gonorrhea infection has also decreased by 5%; however, an increase of 4% was seen in men. In 2010 the rates of primary and secondary syphilis experienced their first decline in 10 years; however, from 2011 to 2013 the rates have increased by more than 20%.
Individuals at the highest risk for contracting an STI are sexually active young adults between the ages of 18 and 25. Other important risk factors are the number of sexual partners, new sex partners, use of illicit drugs, admission to a correctional facility, and a prior history of STI. A newly described risk factor for STI is the use of erectile dysfunction medications in older men. A review of men prescribed ED medication found a 2- to 3-fold increase in the rate of STIs in men taking erectile dysfunction medications compared with men not taking these medications. Recent travel is also an important risk factor for the acquisition of STIs and has been seen in approximately 2.9% of illnesses in returning travelers.
Primary prevention of STIs begins with recognizing the risk behaviors of individual patients and counseling on changing these behaviors to prevent the acquisition of STIs. The US Preventive Services Task Force (USPSTF) recommends high-intensity behavioral counseling for all sexually active adolescents and adults. This involves routinely obtaining a sexual history on all patients and a discussion of behavior modifications and changes to at-risk practices. These counseling interventions have demonstrated efficacy in reducing acquisition rates of syphilis, Chlamydia, gonorrhea, and trichomoniasis. The CDC also promotes obtaining a sexual history focusing on the 5Ps: Partner(s), Prevention of pregnancy, Protection form STIs, sexual Practices, and Past history of STIs. These questions can lead to conversations about primary and secondary prevention. Prevention counseling should be provided in a safe, nonjudgmental, and empathetic environment.
This review focuses on the common causes of STIs. The focus is on the causes of ulcerative and nonulcerative diseases, condyloma, and a discussion on partner notification and treatment.
Infections that cause ulcers
Syphilis
The incidence of syphilis in the United States peaked in the 1940s, with an incidence of 66.9 cases per 100,000 persons ( Table 1 ). Aggressive public health interventions, including treatment with penicillin and contact tracing, led to a significant decrease in the incidence of primary and secondary syphilis. By the late 1990s, there was a significant decline in the incidence of syphilis, with a rate of 2.1 cases per 100,000 persons. Since 2011 there has been a steady increase in the incidence of syphilis, and in 2014 there was a rate of 5.5 cases per 100,000 persons. Approximately 75% of all primary and secondary syphilis cases have been diagnosed in MSM.
| Disease/Etiologic Agent | Ulcer Characteristics | Incubation | Pain | Adenopathy | Treatment | Alternative Treatment |
|---|---|---|---|---|---|---|
| Indurated, smooth borders | 9–90 d | Painless | Firm, painless; bilateral | See Table 2 | See Table 2 |
| Multiple small ulcers; erythematous base | 2–7 d | Painful | Reactive Painful | See Table 3 | See Table 3 |
| Sharply circumscribed, ragged edges; not indurated; gray, yellow base; multiple | 3–10 d | Very painful | Usually unilateral; may suppurate or rupture | Azithromycin, 1g po × 1 Patients should be re-examined 3–7 d after treatment to ensure improvement in symptoms. | Ceftriaxone, 250 mg IM × 1 |
| Rare; small and shallow | 5–21 d | Painless | Matted in clustered; unilateral or bilateral; sinus tracts | Doxycycline, 100 mg po bid × 21 days | Erythromycin, base 500 mg po q 6 h × 21 d |
| Extensive, progressive granulation-like tissue; rolled edges | 7–90 d | Usually painless | Pseudobuboes | Doxycycline, 100 mg po bid Treatment should be for at least 3 wk or until all lesions have completely healed, whichever is longer | Azithromycin, 1g po weekly OR Ciprofloxacin, 750 mg po bid OR Trimethoprim-suflamethoxazole, 1 DS tablet bid |
Clinical presentation
Syphilis is caused by the spirochete, Treponema pallidum pallidum . Transmission occurs through contact with active lesions, infected body fluids, or blood transfusion or can be acquired in utero.
Once infection is established, there is rapid systemic dissemination, including to the central nervous system. The incubation period is approximately 21 days, at which time a single, painless chancre develops at the site of inoculation. These lesions often are unnoticed, particularly in women and MSM who are practicing receptive anal intercourse, where the lesions are in locations that are difficult to visualize. The lesion, which may be accompanied by regional lymphadenopathy, fever, or malaise, is often self-limited and resolves within a few days to weeks (3–90 days). Untreated, the infection may progress to a secondary and tertiary phase.
Secondary syphilis presents as skin and mucous membrane lesions or rash, approximately 4 to 10 weeks after inoculation. The rash is macular and nonpruritic and may be associated with regional lymphadenopathy or systemic symptoms. Lesions are typically 5 to 10 mm and red in color and as they progress may become papular or papulosquamous ( Fig. 1 ). Approximately 50% to 80% of cases have the rash on the palms and soles. Like the primary chancre, the rash resolves with or without treatment and the infection enters a latent phase.
Latency is divided into early (infection acquired within the previous year) or late (infection acquired >1 y or unknown duration) phases. During this latent stage, most persons are not infectious, the major exception pregnant women who can pass the infection vertically to their fetus. Most patients with latent syphilis stay in this stage indefinitely; however, up to 25% of patients with untreated syphilis go on to develop tertiary manifestations.
The primary manifestations of tertiary syphilis include cardiovascular disease, gummatous disease, and/or neurologic manifestations. Cardiovascular complications can present 10 to 30 years after infection and can lead to aoritis, angina from coronary ostitis, aortic regurgitation, or aortic aneurysm. Gummas can present in any organ and lead to serious complications depending on the organ involved, the most severe being the central and peripheral nervous systems.
Neurosyphilis can occur at any stage of infection, including primary infection. Early neurosyphilis is characterized by meningovascular disease, including meningitis, strokes, seizures, myelopathy, cranial nerve palsy, and vestubular and ocular disease (retinitis). Late neurosyphilis affects the brain and spinal cord parenchyma, presenting as dementia, tabes dorsalis, general paresis, or sensory ataxia.
Diagnostic testing
When a diagnosis of syphilis is suspected, a detailed sexual history and physical examination are necessary. Physical examination should focus on dermatologic, neurologic, ocular, auditory, and vestibular manifestations of syphilis. Diagnosis can be made using dark-field microscopy of a scraping of the ulcer or rash. This testing modality has 75% to 95% sensitivity, depending on the investigator, and requires specific staining and microscopes.
Serologic testing remains the standard for diagnosis, and it is recommended that all patients with concern for syphilis undergo serologic testing. Most testing involves a 2-step process: first, nontreponemal testing with the rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL), and second, followed by confirmatory treponemal antibody testing of human IgM and IgG antibodies to T pallidum with, fluorescent treponemal antibody absorbed tests. Nontreponemal antibody titers peak during secondary syphilis without treatment and then gradually decline. Approximately 30% of patients become seronegative over their lifetimes without treatment. Appropriate and successful treatment is considered if there is a 4-fold, or 2-dilution, decline in titers at 6 and 12 months post-treatment (example, RPR 1:16–1:4). A small percentage of patients become serofast with an RPR titer that fails to become nonreactive and stays detectable at 1:1 to 1:8 despite adequate therapy. Treatment failure is defined as a lack of 4-fold decline in titers or recurrence of symptoms prior to the first follow-up period at 6 to 12 months. An initial RPR that is greater than or equal to 1:32 and/or the patient with concerning neurologic or ocular symptoms or physical examination inding is suggestive of neurosyphilis. Patients should be referred to an infectious diseases specialist for lumbar puncture with cerebrospinal fluid (CSF) analysis of cell count with differential, total protein, and CSF VDRL or treponemal antibody. Regardless of disease stage, treponemal testing is positive for most patients infected with T pallidum and remains positive.
Treatment
Penicillin remains the first-line therapy for all stages of syphilis ( Table 2 ). Primary, secondary, and early latent syphilis are all treated with a single intramuscular dose of 2.4 million units of penicillin G benzathine. Late latent syphilis, syphilis of unknown duration, and tertiary syphilis are treated with 2.4 million units penicillin G benzathine intramuscularly, weekly, for 3 consecutive weeks. For patients with confirmed neurosyphilis, ocular syphilis, or auditory syphilis, treatment should be aqueous crystalline penicillin G intravenously, daily, for 10 to 14 days, followed by penicillin G benzathine 2.4 million units, intramuscularly, weekly, for 1 to 3 weeks. All patients should be warned about a possible Jarisch-Herxheimer reaction 2 to 24 hours after treatment.
| Stage | Treatment (Drug of Choice) | Treatment (Alternative) |
|---|---|---|
| Primary syphilis Secondary syphilis Early latent syphilis | PCN G benzathine, 2.4 million units IM once | Doxycyline, 100 mg bid × 14 d a |
| Late latent syphilis a Tertiary syphilis a | PCN G benzathine, 2.4 million units IM weekly for 3 wk | Doxycyline, 100 mg bid × 4 wk a |
| Neurosyphilis b , c | PCN G, 3–4 million units IV q 4 h for 14 d | PCN G procaine, 2.4 million units IM daily PLUS probenecid 500 mg qid × 10–14 d OR Ceftriaxone, 2g IV daily for 14 d |
a Not recommended in pregnancy.
b Patients allergic to penicillin should be desensitized and treated with penicillin.
c Fourteen days of IV PCN should be followed by 1 to 3 doses of PCN G benzathine weekly for neurosyphilis.
If patients are known to have an allergy to penicillin, treatment of primary, secondary, or early latent syphilis should be with doxycycline for 14 days or ceftriaxone for 8 to 10 days, but treatment failure rates may be high. For late latent syphilis, treatment with doxycycline is extended for a total of 28 days. Pregnant patients should undergo desensitization to penicillin in an intensive care unit and then complete therapy as indicated based on stage of disease.
Herpes Simplex Virus
Epidemiology
It is estimated that more than 50 million people in the United States have genital herpes, caused most often by herpes simplex virus (HSV)-2 but increasingly by HSV-1. Infection is lifelong, and the spectrum of disease is broad, ranging from asymptomatic to recurrent ulcerative disease. Seroprevalence studies reveal an overall decrease in the prevalence of HSV-2; however, most people have never been clinically diagnosed with HSV-2 infection. Transmission is likely occurring from chronic shedding in asymptomatic individuals.
Clinical presentation
Primary genital HSV infection has a broad range of clinical symptoms. Most often, primary infection presents with painful genital or anal vesicles or ulcers and may be associated with dysuria, fever, and tender inguinal lymphadenopathy. Some individuals may have mild symptoms or may be completely asymptomatic. The average incubation period after exposure is 4 days.
A minority of patients develop extragenital complications during primary infection. In 1 series, the most common extragenital complications were development of extragenital lesions, secondary yeast infections, aseptic meningitis, and sacral autonomic dysfunction. Rarely, infection may result in viremia and disseminated disease manifesting as pneumonitis, hepatitis, meningitis, and/or encephalitis. Recurrent HSV-2 meningitis, called Mollaret meningitis, is associated with a lymphocytic pleocytosis and normal glucose in the CSF and is not associated with concomitant genital lesions. HSV can also cause proctitis, particularly in MSM or in those practicing receptive anal intercourse. In a series of proctitis in MSM in San Francisco, HSV was the cause of the proctitis in 13% of the individuals tested.
Diagnostic testing
Diagnosis of genital herpes is most often made clinically. Painful vesicular lesions that do not follow a dermatomal distribution are pathognomonic. To confirm the diagnosis, and to distinguish between HSV-1 and HSV-2, a vesicular lesion can be unroofed and the base swabbed for HSV-1– and HSV-2–specific polymerase chain reaction, direct fluorescent antibody testing, or viral culture. Failure to detect HSV from a vesicle likely represents sampling error or low viral shedding and not absence of infection when clinical suspicion remains high. Serologic screening at time of primary infection has little utility in making the diagnosis of genital herpes. Serologic testing may be useful to aid in the diagnosis of recurrent genital ulcers that do not respond to antiviral therapy, determine susceptibility to infection in a sexual partner of a person with documented HSV infection, or identify asymptomatic infection in a pregnant women. Routine serologic screening for HSV-2 infection is not recommended due to the possible high false-positive rate of testing in a low-prevalence population.
Treatment
Primary infection can result in a prolonged clinical illness with severe genital ulcers and possible neurologic involvement. All patients with first episodes of genital herpes should receive oral antiviral therapy. Topical therapy is ineffective and not recommended. Oral antivirals approved for the treatment of HSV include acyclovir, valacyclovir, and famciclovir. These agents can be used to treat primary or recurrent infections and may also be used for suppressive therapy ( Table 3 ). Recurrent outbreaks are less frequent with HSV-1 infection. Intermittent asymptomatic shedding can occur with genital HSV-2 infection. Antiviral therapy taken at the onset of recurrent symptoms can ameliorate or shorten the duration of the outbreak. In those patients with frequent outbreaks, chronic suppression should be discussed.
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