Approach to the Patient with a Sexually Transmitted Infection

Definition

Sexually transmitted infections (STIs) include a wide variety of organisms that are transmitted through intimate contact involving skin or mucosal surfaces of the oropharynx, vagina, penis, and rectum. STIs can generally be divided into five broad categories (syndromes): urethritis, genital ulcers, epithelial cell disorders, vaginal discharge, and ectoparasites ( Table 264-1 ). Gender inclusive models ( Chapter 215 ) and programs of care are recommended for all persons who would benefit from such services.

Epidemiology

The interaction between the host and the sexually transmitted pathogen plays a critical role, and characteristic tissue changes offer clues about etiology. Several sexually transmitted pathogens cause local inflammation only ( Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis ), with the potential for local tissue invasion ( N. gonorrhoeae , C. trachomatis ) or systemic dissemination ( N. gonorrhoeae ). Some sexually transmitted pathogens cause tissue ulceration ( Treponema pallidum , Haemophilus ducreyi , herpes simplex viruses 1 and 2, Klebsiella granulomatis ). Human papillomaviruses cause epithelial cell changes and predispose to neoplasm. Several sexually transmitted pathogens (human immunodeficiency virus [HIV], hepatitis B and C viruses, cytomegalovirus) routinely enter through the genital tract without causing any local changes.

Other important systemic diseases that can be acquired through sexual transmission include Zika virus, Ebola virus, Lassa fever, and monkeypox ( Chapters 343 , 351 , and 352 ). Although these infections can present with genital cutaneous lesions that can be confused with herpes simplex virus, they can cause systemic signs and symptoms that can be fatal.

Sexually transmitted infections are among the most common infections worldwide, but most are never reported. The World Health Organization (WHO) estimates that nearly 1 million people worldwide become infected every day with any of four curable sexually transmitted infections: chlamydia, gonorrhea, syphilis, and trichomoniasis. Each year, an estimated 2.5 million incident cases of gonorrhea, chlamydia, and syphilis are reported in the United States alone. However, the total estimated number of cases of all sexually transmitted infections is likely much greater because of under-reporting and because many infections are subclinical and may escape detection. Sexually transmitted infections are generally transmissible whether they are symptomatic or asymptomatic.

Despite efforts to control the epidemic of sexually transmitted infections, the numbers of new infections continue to grow. This epidemic disproportionately impacts specific populations and geographies, sometimes leading to long-term health consequences such as infertility, poor birth outcomes, cancer, and HIV infection. In the United States, social determinants of health contribute to an unequal burden of sexually transmitted infections in Black, American Indian/Alaska Native, and Latinx communities ( Chapter 4 ).

Chlamydia ( Chapter 294 ), gonorrhea ( Chapter 275 ), and syphilis ( Chapter 295 ) are reportable to the U.S. Centers for Disease Control and Prevention (CDC). Overall, primary and secondary syphilis rates have increased every year since 2000 and increased by 6.8% from 2019 to 2020. Although rates of syphilis are lower among women compared with men, rates in women have increased nearly 150% from 2016 to 2020, and rates of congenital syphilis increased by 250% during that time period. Men who have sex with men account for almost 60% of syphilis cases among men. For gonorrhea, the overall rate is about 150 cases per 100,000 population among women and 225 cases per 100,000 in men, but rates in men and women ages 20 to 24 years are closer to 750 cases per 100,000.

Emerging pathogens also must be considered in certain groups of patients. Some of these pathogens are asymptomatic but are of public health significance (e.g., Ebola [ Chapter 351 ], Zika [ Chapter 352 ] viruses in genital secretions), whereas others represent relatively newly recognized pathogens (e.g., Neisseria meningitidis urethritis [ Chapter 274 ] and monkeypox [ Chapter 343 ]).

Seroprevalence data and national surveys suggest a high burden of viral sexually transmitted infections. Antibodies to herpes simplex virus 2 (HSV-2) are found in the serum of about 12% of the population (ages 14 to 49 years), with seropositivity more frequent in non-Hispanic Black Americans (about 35%) compared with non-Hispanic Whites (about 8%), and in women (about 16%) compared with men (about 8%).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic significantly impacted the availability of services for patients who have sexually transmitted infections, especially in urban settings. The longer-term ramifications of missed opportunities for screening and intervention remain to be seen.

The spread of sexually transmitted infections depends on the organism, the host, the length of time an infected person remains contagious, and the number of people exposed. These parameters can be summarized as:

where R _o is the basic reproductive rate of an infection, or the mean number of secondary cases a typical single infected person will cause in a population; B is the efficiency of transmission; D is the duration of infectiousness; and C is the number of sexual partners.

Pathobiology

Sexually transmitted pathogens depend entirely on human-human transmission, although T. vaginalis may have some inanimate sources. The efficiency of transmission reflects the infectiousness of the index case (which depends on the concentration and phenotype of the organism in the genital tract) and the susceptibility of the sexual partner (which reflects the resistance of the host, whether it is hereditary, acquired, or innate). Because immunity to STIs is rare, reinfections are common, and vaccines have been developed only for hepatitis A, hepatitis B, and human papillomavirus.

Each sexually transmitted organism produces a characteristic syndrome because each pathogen has a proclivity for one or more tissues and, when symptomatic, can evoke a predictable inflammatory response. For example, gonococci ( Chapter 275 ) that infect the male urethra generally produce an intense neutrophilic response that leads to a purulent discharge and pain with urination, whereas C. trachomatis ( Chapter 294 ) is less likely to produce such a response in the same tissue and is more likely to produce a mild, watery discharge or no symptoms at all.

Because sexually transmitted infections are more prevalent in certain geographies and populations, coinfections are common. Detection of one sexually transmitted organism should lead to other tests. Sexually transmitted pathogens also can be synergistic: for example, sexually transmitted infections also contribute to the acquisition and transmission of HIV and hamper efforts to prevent its transmission. Genital ulcers disrupt the genital mucosal epithelium and allow the entry of HIV. Inflammation caused by ulceration recruits macrophages and lymphocytes, thereby increasing the number of target cells for HIV and the number of receptors per cell. Sexually transmitted infections also can increase the HIV viral load in genital secretions, including semen and vaginal secretions, thereby contributing to a greater risk of transmitting HIV.

Diagnosis

Treatment And Prevention

Clinical Manifestations and Diagnosis

Urethritis is characterized by some combination of urethral discharge and dysuria, but prostatitis ( Chapter 114 ) can cause similar complaints. Women with urethritis typically have some combination of dysuria and pyuria, which must be differentiated from bacterial cystitis ( Chapter 263 ).

Urethritis is diagnosed when one or more of the following are demonstrated: (1) mucopurulent or purulent urethral discharge, (2) Gram stain of urethral secretions demonstrating two or more leukocytes per oil immersion microscopic field, (3) positive leukocyte esterase test result on first-void urine, or (4) microscopic examination of first-void urine demonstrating 10 or more leukocytes per high-power field. If no urethral discharge can be expressed from the urethral meatus, a calcium alginate swab can be inserted 5 mm into the urethra; the material collected is transferred to a slide by rolling the swab along the glass.

Urethritis is caused by a limited group of pathogens (see Table 264-1 ) that may be difficult to visualize microscopically or to grow in culture. Nevertheless, specific diagnosis may enhance the management of sexual partners, and the results from such tests should be reported to the health department.

A Gram stain of urethral discharge is a simple and rapid diagnostic test to document both urethritis and possible gonococcal infection ( Chapter 275 ), which is characterized by the detection of leukocytes containing intracellular gram-negative diplococci ( Fig. 275-1 ). Because confirmation of gonococcal urethritis does not exclude concomitant infection with Chlamydia or Mycoplasma , NAATs, which are highly sensitive and specific for the detection of these and other organisms, are routinely performed on the urethral discharge owing to the high probability of coinfection. However, clinicians should use caution in relying solely on NAATs for diagnosing gonorrhea because it does not always identify other sexually transmitted Neisseria species, such as Neisseria meningitidis.

Nucleic acid amplification tests for gonorrhea, Chlamydia , and Trichomonas also can be applied to first-void urine samples (the meatus is intentionally not cleaned so that the urine is contaminated with these organisms), urethral swab material, or vaginal swab material. Extra-genital (e.g., rectal and throat swabs) NAATs are recommended for men who have sex with men or women with reported exposures, since urine-based and cervicovaginal testing alone can miss a large proportion of infected individuals.

Treatment

Genital Herpes

Genital herpes ( Chapter 345 ), which usually develops after an incubation period of less than 21 days, arises as clustered vesicles on an erythematous base. The vesicles become pustular and then rupture to form shallow, painful ulcers that may coalesce. The ulcers heal by crusting over, and the process is usually completed 2 to 3 weeks after the initial lesions appear. In the recent monkeypox outbreak, the lesions were initially confused with the vesicles of herpes simplex virus. Recurrences proceed through the same stages but generally persist only about 5 to 7 days. The first (incident) episode of HSV-2 infection may be accompanied by systemic signs and symptoms including fever and headache, the latter reflecting the spread of HSV to the central nervous system. HSV-2 can cause recurrent meningitis that may occur coincident with reactivation of the genital lesions.

About 20% of infected individuals manifest the classic genital presentation, 60% have mild and atypical signs and symptoms, and the remaining 20% are completely asymptomatic. Viral shedding occurs more often in symptomatic individuals (20% of days) compared with asymptomatic individuals (10% of days), thereby posing an ongoing risk to sexual partners. Nucleic acid testing of swabs of lesions has a 97% sensitivity for detecting herpes virus. However, serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Treatment with antiviral medications can shorten the duration of symptoms and may be helpful for preventing recurrence of HSV-2 ( Table 264-3 ). Counseling for patients should include a discussion of the risk of shedding, disclosure, and the avoidance of sex in the viral prodrome or during outbreaks.

Syphilis

The ulcerative lesion of syphilis ( Chapter 295 and Fig. 295-1 )—the chancre—is indurated and typically painless. Some patients may have multiple ulcers rather than a single chancre. Swabs from a genital ulcer should be collected and examined by dark-field microscopy; the finding of motile spirochetes is diagnostic for syphilis. When darkfield microscopy is not available, primary syphilis can be diagnosed with serologic testing, but the nontreponemal and treponemal antibody tests may be negative in early primary infection. Secondary syphilis results when the spirochetes spread systemically, thereby leading to a characteristic maculopapular rash involving the palms and soles, alopecia, oral mucous patches, or condyloma latum.

All patients who present with a sexually transmitted infection must have serologic screening ( E-Fig. 264-1 ) for syphilis. (e.g., rapid plasma reagin test, Venereal Disease Research Laboratory [VDRL] test, toluidine red unheated serum test [TRUST]). If reactive, the diagnosis must be confirmed with a more specific treponemal antibody test (microhemagglutination assay– T. pallidum , fluorescent treponema antibody test). However, some large laboratories have switched to the reverse syphilis screening algorithm using newer automated treponemal tests for initial testing followed by a nontreponemal test ( Chapter 295 ).

All patients diagnosed with syphilis should be questioned about ocular symptoms and symptoms suggestive of neurosyphilis; ocular and neurosyphilis require 14 days of intravenous aqueous penicillin G ( Table 295-4 ). Late latent syphilis and syphilis of unknown duration are managed with three weekly injections of intramuscular penicillin.