Sexually transmitted infections (STIs) are infectious diseases that are commonly acquired through sexual contact (Table 53-1). They may also be contracted by other routes such as through blood, blood products, perinatal transmission, and autoinoculation. STI is becoming the more common term used for sexually transmitted disease.

TABLE 53-1

CAUSES OF SEXUALLY TRANSMITTED INFECTIONS

Sexually Transmitted Infection	Cause
Bacterial
Gonorrhea	Neisseria gonorrhoeae
Syphilis	Treponema pallidum
Nongonococcal urethritis (NGU), cervicitis, lymphogranuloma venereum	Chlamydia trachomatis
Viral
Genital herpes	Herpes simplex virus (HSV)
Genital warts. Cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers	Human papillomavirus (HPV)
Human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS)	HIV virus (see Chapter 15)
Hepatitis B and C	Hepatitis B and C viruses (see Chapter 44)
Encephalitis, esophagitis, retinitis, pneumonitis in immunocompromised patients	Cytomegalovirus (CMV)

Most infections start as lesions on the genitalia and other sexually exposed mucous membranes. Wide dissemination to other areas of the body can then occur. A latent or subclinical phase is present with all STIs. This can lead to a long-term persistent infection and the transmission of disease from an asymptomatic (but infected) person to another person. Having one STI increases the risk of acquiring another. A person can have different STIs at the same time.

In the United States all cases of gonorrhea and syphilis, and in most states chlamydial infection, must be reported to the state or local public health authorities for purposes of surveillance and partner notification. In spite of this requirement, many cases of these infections go unreported. An estimated 65 million Americans are currently infected with one or more STI. Every year an additional 19 million Americans are newly infected with an STI. About 50% of these new cases are in persons 15 to 24 years old.¹

The most commonly diagnosed STIs are discussed in this chapter. Human immunodeficiency virus (HIV) infection is discussed in Chapter 15. Hepatitis B and C infections are discussed in Chapter 44.

Factors Affecting Incidence of Sexually Transmitted Infections

Many factors contribute to the current STI rates. Earlier reproductive maturity and increased longevity have resulted in a longer sexual life span. The increase in the total population has resulted in an increase in the number of susceptible hosts. Other factors include greater sexual freedom, lack of barrier methods (e.g., condoms) during sexual activity, and the media’s increased emphasis on sexuality. Substance abuse contributes to unsafe sexual practices. In addition, increased leisure time, more national and international travel, and urbanization have brought together people with varying social behaviors and value systems.

Changes in the methods of contraception are also reflected in the incidence of STIs. The condom is considered to be the best form of protection (other than abstinence) against STIs. Although condom use has increased, condoms are still not used frequently in the general population.² Commonly used oral contraceptives cause the secretions of the cervix and the vagina to become more alkaline. This change produces a more favorable environment for the growth of organisms that cause STIs at these sites. Women who take oral contraceptives may have a lower risk of pelvic inflammatory disease (PID) as a result of the ability of the cervical mucus to act as a barrier against bacteria. However, the proliferation of Chlamydia organisms, the leading cause of nongonococcal PID, may be enhanced by oral contraceptive use.

Whether or not intrauterine device (IUD) users are at increased risk of PID is controversial, but it is clear that IUDs confer no protection against STIs. Long-acting contraceptives such as medroxyprogesterone (Depo-Provera) also offer no protection against STIs. Although these methods do not prevent transmission from partner to partner, they do prevent pregnancy and, therefore, transmission of the infection to the fetus.

Bacterial Infections

Gonorrhea

Gonorrhea is the second most frequently reported STI in the United States (chlamydial infections are the most common). In 2009 the gonorrhea rates were the lowest since recording of rates began. Since that time gonorrhea rates have increased slightly. A total of 309,341 cases of gonorrhea have been reported in the United States.³ Gonorrhea rates are highest in adolescents of all racial and ethnic groups and among African Americans. Most states have enacted laws that permit examination and treatment of minors without parental consent.

Cultural & Ethnic Health Disparities

Sexually Transmitted Infections

• Chlamydial infection: African Americans are 48% of cases.

• Syphilis: African Americans are 46% of cases, a rate 60 times higher than that of whites.

• HSV-2: More common in African Americans (46%) than whites (18%).

• Gonorrhea: African Americans are 77% of reported cases.

• All STIs: Hispanics have four times higher rate than whites.

HSV-2, Herpes simplex virus type 2.

Etiology and Pathophysiology

Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative diplococcus. The infection is spread by direct physical contact with an infected host, usually during sexual activity (vaginal, oral, or anal). Mucosal tissues in the genitalia (urethra in men, cervix in women), rectum, and oropharynx are especially sensitive to gonococcal infection. The delicate gonococcus is easily killed by drying, heating, or washing with an antiseptic solution. Consequently, indirect transmission by instruments or linens is rare.

The incubation period is 3 to 8 days. The infection confers no immunity to subsequent reinfection. Gonococcal infection elicits an inflammatory response, which, if left untreated, leads to the formation of fibrous tissue and adhesions. This fibrous scarring is responsible for many complications in women such as strictures and tubal abnormalities, which can lead to tubal pregnancy, chronic pelvic pain, and infertility.

Clinical Manifestations

Men.

The initial site of infection in men is usually the urethra. Symptoms of urethritis consist of dysuria and profuse, purulent urethral discharge developing 2 to 5 days after infection (Fig. 53-1). Painful or swollen testicles may also occur. Men generally seek medical evaluation early in the infection because their symptoms are usually obvious and distressing. It is unusual for men with gonorrhea to be asymptomatic.⁴

FIG. 53-1 Profuse, purulent drainage in a patient with gonorrhea.

Women.

Many women who contract gonorrhea are asymptomatic or have minor symptoms that are often overlooked, making it possible for them to remain a source of infection. A few women may complain of vaginal discharge, dysuria, or frequency of urination. Changes in menstruation may be a symptom, but the women often disregard these changes. After the incubation period, redness and swelling occur at the site of contact, which is usually the cervix or urethra (Fig. 53-2). A greenish yellow purulent exudate often develops with a potential for abscess formation. The infection may remain local or can spread by direct tissue extension to the uterus, fallopian tubes, and ovaries. Although the vulva and vagina are uncommon sites for a gonorrheal infection, they may become involved when little or no estrogen is present, as in prepubertal girls and postmenopausal women. Because the vagina acts as a natural reservoir for infectious secretions, transmission is often more efficient from men to women than it is from women to men.

FIG. 53-2 Endocervical gonorrhea. Cervical redness and edema with discharge.

General.

Anorectal gonorrhea may be present, usually as a result of anal intercourse. Symptoms may include mucopurulent anal discharge, bleeding, and tenesmus.⁵ Most patients with anorectal infections and infections in the throat have few symptoms. A small percentage of individuals develop gonococcal pharyngitis from orogenital sexual contact. When the gonococcus can be demonstrated by a laboratory culture, individuals of either gender are infectious to their sexual partners.

Complications

Because men often seek treatment early in the course of the infection, they are less likely to develop complications. The complications that do occur in men are prostatitis, urethral strictures, and sterility from orchitis or epididymitis. Because women who are asymptomatic seldom seek treatment, complications are more common and usually constitute the reason for seeking medical attention. PID, Bartholin’s abscess, ectopic pregnancy, and infertility are the main complications of gonorrhea in women. A small percentage of infected persons, mainly women, may develop a disseminated gonococcal infection (DGI). In DGI the appearance of skin lesions, fever, arthralgia, arthritis, or endocarditis usually causes the patient to seek medical help (Fig. 53-3).

FIG. 53-3 Skin lesions with disseminated gonococcal infection. A, On the hand. B, On the fifth toe.

Neonates can develop a gonococcal infection during delivery from an infected mother. Untreated infected infants develop permanent blindness. Almost all states have a health department regulation or law requiring the use of a prophylactic drug such as erythromycin ophthalmic ointment or silver nitrate aqueous solution in the eyes of all newborns. Therefore gonorrheal eye infections in newborns (ophthalmia neonatorum) are relatively rare today.

Diagnostic Studies

For men, a presumptive diagnosis of gonorrhea is made if there is a history of sexual contact with a new or infected partner followed within a few days by a urethral discharge. Typical clinical manifestations, combined with a positive finding on a Gram-stained smear of the purulent discharge from the penis, give an almost certain diagnosis. A culture of the discharge is indicated for men whose smears are negative in the presence of strong clinical evidence. The nucleic acid amplification test (NAAT) (using ligase or polymerase chain reaction) is a nonculture test with sensitivity similar to culture tests for N. gonorrhoeae. It can be done on a wide variety of samples, including vaginal, endocervical, urethral, and urine specimens.⁶

For women, making a diagnosis of gonorrhea on the basis of symptoms is difficult because most women are symptom free or have complaints that may be confused with other conditions. Smears and purulent discharge do not establish a diagnosis of gonorrhea because the female genitourinary tract normally harbors a large number of organisms that resemble N. gonorrhoeae. A culture must be performed to confirm the diagnosis. Although the cervix is the most common site of sampling, specimens for culture may also be taken from the urethra, anus, or oropharynx. A urine specimen can reveal gonorrhea if it is present in the cervix or urethra.

Gender Differences

Sexually Transmitted Infections

Men	Women
• Syphilis more common, especially in men who have sex with men • More likely to be symptomatic • Easier to diagnose because of less complex anatomy	• Chlamydial infection three times more common • Gonorrhea more common • HSV-2 more common • Have more frequent and serious complications related to STIs (e.g., pelvic inflammatory disease)

HSV-2, Herpes simplex type 2.

Collaborative Care

Drug Therapy.

Because of a short incubation period and high infectivity, treatment is generally instituted without awaiting culture results. The treatment of gonorrhea in the early stage is curative with a cephalosporin antibiotic. Treatment for gonorrhea is an intramuscular (IM) dose of ceftriaxone (Rocephin) or cefixime (Suprax) orally (Table 53-2).

TABLE 53-2

COLLABORATIVE CARE
Gonorrhea

Diagnostic

History and physical examination

Gram-stained smears of urethral or endocervical exudate

Culture for Neisseria gonorrhoeae

Nucleic acid amplification test (NAAT) to detect N. gonorrhoeae

Testing for other STIs (syphilis, HIV, chlamydial infection)

Collaborative Therapy

Uncomplicated gonorrhea: ceftriaxone (Rocephin) IM or cefixime (Suprax) orally

If chlamydial infection is not ruled out: azithromycin (Zithromax) or doxycycline (Vibramycin)

Treatment of sexual contacts

Instruction on abstinence from sexual intercourse and alcohol during treatment

Reexamination if symptoms persist or recur after completion of treatment

Source: Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines, 2010. Retrieved from www.cdc.gov/STD/treatment.

Over the years, N. gonorrhoeae has developed a resistance to multiple classes of antimicrobial drugs, including fluoroquinolones (ciprofloxacin [Cipro], ofloxacin [Floxin], levofloxacin [Levaquin]) and tetracyclines (doxycycline [Vibramycin]). Gonococcal resistance to cephalosporin has recently been reported.⁷

The high frequency (up to 20% in men and 40% in women) of coexisting chlamydial and gonococcal infections has led to the addition of azithromycin (Zithromax) or doxycycline to the treatment regimen. Patients with coexisting syphilis are likely to be treated with the same drugs used for gonorrhea.

Drug Alert

Doxycycline (Vibramycin)

• Patients on this drug should avoid unnecessary exposure to sunlight.

• Do not take with antacids, iron products, or dairy products.

All sexual contacts of patients with gonorrhea must be evaluated and treated to prevent reinfection after resumption of sexual relations. The “ping-pong” effect of reexposure, treatment, and reinfection can end only when infected partners are treated simultaneously. Additionally, counsel the patient to abstain from sexual intercourse and alcohol during treatment. Sexual intercourse allows the infection to spread and can delay complete healing. Alcohol has an irritant effect on the healing urethral walls. Caution men against squeezing the penis to look for further discharge. Reinfection, rather than treatment failure, is the main cause of infections after treatment has ended.

TABLE 53-3

STAGES OF SYPHILIS

Manifestations	Communicability
Primary
Chancre (painless indurated lesion of penis, vulva, lips, mouth, vagina, and rectum) (Fig. 53-4) occurs 10 to 90 days after inoculation. Regional lymphadenopathy (draining of the microorganisms into the lymph nodes). Genital ulcers. Duration of stage: 3-8 wk	Exudate from chancre highly infectious; blood is infectious. Most infectious stage, but transmission can occur at any stage if there are moist lesions.
Secondary
Occurs a few weeks after chancre appears. Systemic manifestations: flu-like symptoms (e.g., malaise, fever, sore throat, headaches, fatigue, arthralgia, headache, generalized adenopathy). Cutaneous lesions bilateral. Symmetric rash that begins on the trunk and involves the palms and soles. Mucous patches in the mouth (Fig. 53-5), tongue, or cervix. Condylomata lata (moist, weeping papules) in the anal and genital area. Weight loss, alopecia. Duration of stage: 1-2 yr	Exudate from skin and mucous membrane lesions highly infectious.
Latent
Absence of signs or symptoms. Diagnosis based on positive specific treponemal antibody test together with normal CSF and absence of clinical manifestations. Duration of stage: Throughout life or progression to late stage	Noninfectious after 4 yr. Possible placental transmission. Almost 25% of persons with latent syphilis develop late syphilis, in some cases many years later.
Late (tertiary)*
Appearance 3-20 yr after initial infection. Gummas (chronic, destructive lesions affecting any organ of body, especially skin, bone, liver, mucous membranes) (Fig. 53-6). Cardiovascular: Aneurysms, heart valve insufficiency, heart failure, aortitis. Neurosyphilis: General paresis (personality changes from minor to psychotic, tremors, physical and mental deterioration), tabes dorsalis (ataxia, areflexia, paresthesias, lightning pains, damaged joints), speech disturbances. Duration of stage: Chronic (without treatment), possibly fatal	Noninfectious. Spinal fluid possibly containing organism.

CSF, Cerebrospinal fluid.

^*Several forms such as cardiovascular syphilis and neurosyphilis occur together in approximately 25% of untreated cases.

Complications

Complications of the disease occur mostly in late syphilis. The gummas of benign late syphilis may produce irreparable damage to bone, liver, or skin. In cardiovascular syphilis, the resulting aneurysm may press on structures such as the intercostal nerves, causing pain. The possibility of a rupture exists as the aneurysm increases in size. Scarring of the aortic valve results in aortic valve insufficiency and eventually heart failure.

Neurosyphilis causes degeneration of the brain with mental deterioration. Problems related to sensory nerve involvement are a result of tabes dorsalis (progressive locomotor ataxia). There may be sudden attacks of pain anywhere in the body, which can confuse the diagnosis with other conditions. Loss of vision and sense of position in the feet and legs can also occur. Walking may become even more difficult as joint stability is lost. (Late syphilis is also discussed in Chapter 59.)

Diagnostic Studies

The first step in diagnosis is to obtain a detailed and accurate sexual history. Asking if the patient has sex with men, women, or both can be more effective than asking directly about sexual orientation, since some men do not identify themselves as gay or homosexual. In addition, inquire about vaginal, oral, or anal sex. A physical examination should be done to identify any suspicious lesions or other significant signs and symptoms. Since syphilis is “the great imitator” of other conditions, it is easily missed. Oral sex is an important transmission route that is sometimes overlooked.

Diagnostic studies for syphilis are presented in Table 53-4. The presence of spirochetes on dark-field microscopy and direct fluorescent antibody (DFA) tests of lesion exudate or tissue can confirm a clinical diagnosis of syphilis. However, syphilis is more commonly diagnosed by a serologic test.⁴ Tests for syphilis may be classified as those performed for screening and those performed for confirmation of a positive screening test. Nonspecific antitreponemal antibodies can be detected by tests such as the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test. These nontreponemal tests are suitable for screening purposes, and usually become positive 10 to 14 days after the appearance of a chancre. The fluorescent treponemal antibody absorption (FTA-Abs) test and the T. pallidum particle agglutination (TP-PA) test detect specific antitreponemal antibodies and are used for confirming the diagnosis.