Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 83. Sexually Transmitted Diseases

Sexually transmitted diseases are relatively common during pregnancy, especially in indigent, urban populations. Screening, identification, education, and treatment are important components of prenatal care for women at increased risk for these infections.

SYPHILIS

Syphilis is caused by the spirochete, Treponema pallidum. The rate of syphilis in the United States in 2006 was 3.3 cases per 100,000 persons. Risk factors associated with syphilis include substance abuse, particularly crack cocaine; prostitution; lack of prenatal care; young age; low socioeconomic status; minority race or ethnicity; and multiple sexual partners.

Maternal Infection

The primary syphilis genital lesion is called a chancre. The chancre is characterized by a painless firm ulcer with raised edges and a granulation base. It persists for 2 to 6 weeks and then heals spontaneously and is often accompanied by nontender, enlarged inguinal lymph nodes.

Approximately 4 to 10 weeks after resolution of the chancre, secondary syphilis usually appears in the form of a highly variable skin rash. Palmar or plantar target-like lesions, alopecia, and mucous patches may be present. In some, lesions are limited to the genitalia where they appear as elevated lesions called condylomata lata. Constitutional symptoms of fever, malaise, arthralgia, and myalgia are common. If not treated, syphilis progresses to an asymptomatic stage. If the duration from infection to diagnosis is less than 12 months and the patient is asymptomatic, a diagnosis of early latent syphilis is made. If the duration is greater than 12 months, a diagnosis of late latent syphilis is given.

Fetal and Neonatal Infection

In the past, syphilis accounted for nearly a third of stillbirths. Syphilis now has a small but persistent role in fetal death, especially before 30 weeks. Spirochetes readily cross the placenta and can result in congenital infection. Because of relative immunoincompetence prior to 18 weeks, the fetus generally does not manifest clinical disease if infected before this time. The frequency of congenital syphilis varies with both the stage and duration of maternal infection. The highest incidence is in neonates born to mothers with early syphilis—primary, secondary, or early latent—and the lowest incidence with late latent disease. Importantly, any stage of maternal syphilis may result in fetal infection.

Diagnosis

Although traditionally diagnosis of syphilis was performed by direct detection using darkfield microscopy, serological testing is now widely used. Screening for syphilis is done using a nontreponemal test. The two most commonly used in the United States are the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests. Each is inexpensive and technically easy to perform. A quantified titer is reported, which often becomes negative after treatment. It is these titers that are followed to determine treatment efficacy. Due to low specificity, a positive nontreponemal test must be confirmed using a treponemal test. The fluorescent treponemal antibody absorption test (FTA-Abs), microhemagglutination assay for antibodies to T. pallidum (MHA-Tp), and the T. pallidum passive particle agglutination (TP-PA) are all acceptable confirmatory tests.

Management

Penicillin remains the treatment of choice. Syphilis therapy during pregnancy has two goals; it is given to eradicate maternal infection and to prevent congenital syphilis. Current treatment regimens (Table 83-1) have been shown to cure early maternal infection and prevent neonatal syphilis in 98 percent of cases. Pregnant women with a history of penicillin allergy should have skin testing to confirm the risk of anaphylaxis. If skin testing is positive, penicillin desensitization is recommended and is followed by benzathine penicillin G treatment. There are no proven alternatives to penicillin therapy during pregnancy at this time. Concomitant infection with human immunodeficiency virus (HIV) does not alter the treatment regimen.

TABLE 83-1. Recommended Treatment for Pregnant Women with Syphilis

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In most women with primary syphilis and about half with secondary infection, penicillin treatment is followed by the Jarisch-Herxheimer reaction. Uterine contractions frequently develop with this reaction, and they may be followed by fetal distress manifested as late fetal heart rate decelerations. Pretreatment ultrasound in pregnancies greater than 24 weeks is useful to detect congenitally infected fetuses. If placental enlargement, polyhydramnios, hepatosplenomegaly, or hydrops is identified, electronic fetal heart rate monitoring is recommended during penicillin treatment.

Follow-up

Sexual contacts within the past 3 months should be evaluated for syphilis and treated presumptively, even if seronegative. Maternal serological titers should be repeated in the third trimester and at delivery to confirm a serological response to treatment or to document reinfection in this high-risk group. A 2-titer (“fourfold”) or greater increase suggests reinfection or treatment failure. For example, an RPR titer that originally was 1:4 and increased to 1:16 suggests reinfection.

GONORRHEA

Gonorrhea results from infection with Neisseria gonorrhoeae. The prevalence during pregnancy is 1 percent. Risk factors include being single, adolescence, poverty, drug abuse, prostitution, other sexually transmitted diseases, and lack of prenatal care. Gonococcal infection is also a marker for concomitant chlamydial infection in up to 40 percent of infected pregnant women. A screening test for gonorrhea is recommended at the first prenatal visit or prior to an induced abortion. In high-risk populations, the Centers for Disease Control and Prevention (CDC) recommends that a repeat culture be obtained after 28 weeks.

Maternal Infection

In most pregnant women, gonococcal infection is limited to the lower genital tract, including the cervix, urethra, and periurethral and vestibular glands. Acute salpingitis is rare. The exception is very early in pregnancy when cervical infection ascends before obliteration of the uterine cavity through fusion of the chorion and decidua, which occurs at 12 weeks. Increased rates of oropharyngeal and anal infections during pregnancy have been reported. Disseminated gonococcal infection may lead to petechial or pustular skin lesions, arthralgias, septic arthritis, or tenosynovitis. Indeed, gonorrhea is the most common cause of arthritis during pregnancy.

Fetal Infection

Gonococcal infection may have deleterious effects on pregnancy outcome in any trimester. There is an association between untreated gonococcal cervicitis and septic abortion. Preterm delivery, prematurely ruptured membranes, chorioamnionitis, and postpartum infection are also more common in women with N. gonorrhoeae detected at delivery. All newborn infants are given prophylaxis, usually with erythromycin ointment, against gonococcal eye infection.

Management

The treatment for uncomplicated gonococcal infections during pregnancy is shown in Table 83-2. Presumptive treatment for Chlamydia trachomatis should be given due to the high coinfection rate unless it is ruled out. Sexual contacts should also be treated. A test-of-cure is unnecessary if symptoms resolve. Disseminated gonococcal infection is treated more aggressively. The CDC (2010) recommends ceftriaxone, 1000 mg intramuscularly or intravenously every 24 hours. These regimens should be continued for 24 to 48 hours after improvement and then therapy changed to an oral agent to complete at least one week of therapy.

TABLE 83-2. Treatment of Uncomplicated Gonococcal Infections during Pregnancy

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CHLAMYDIA

C. trachomatis is an obligate intracellular bacterium that has several serotypes, including those that cause lymphogranuloma venereum (LGV). The most commonly encountered strains are those that cause cervical infection, and this is one of the most common sexually transmitted bacterial diseases in women of reproductive age. Risk factors for chlamydial infection include age less than 25 years, presence or history of other sexually transmitted disease, multiple sexual partners, and a new sexual partner within 3 months.

Maternal Infection

Most pregnant women have subclinical or asymptomatic chlamydial infection. The organism may cause several clinical syndromes that include urethritis, mucopurulent cervicitis, acute urethral syndrome, perihepatitis, conjunctivitis, reactive arthritis, and acute salpingitis. Mucopurulent cervicitis is difficult to classify. It may be secondary to either chlamydial or gonococcal infection, or it may represent the normally increased cervical mucus associated with pregnancy. There is controversy whether chlamydial infection causes preterm delivery, premature rupture of membranes, or excess perinatal mortality.

Neonatal Infection

Perinatal transmission is associated with neonatal conjunctivitis and pneumonia. Ophthalmic chlamydial infections are one of the most common causes of preventable blindness in undeveloped countries, and for this reason, erythromycin eye ointment is routinely given to newborn infants. C trachomatis is a common cause of afebrile pneumonia in infants at 1 to 3 months of age.

Management

The US Preventative Services Task Force (2007) and the CDC recommend prenatal screening at the first prenatal visit for women at increased risk for chlamydial infection and again in the third trimester if the high-risk behavior continues. Currently recommended regimens for treatment of chlamydial infection in pregnant women are shown in Table 83-3. Subsequent chlamydial testing 3 to 4 weeks after completion of therapy is recommended.

TABLE 83-3. Treatment of Chlamydia trachomatis during Pregnancy

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HERPES SIMPLEX VIRUS

Two types of herpes simplex virus (HSV) have been distinguished based on immunological as well as clinical differences. Type 1 (HSV-1) is responsible for most nongenital herpetic infections. In adults, HSV-1 primary infection now involves the genital tract in more than half of new cases of genital herpes. Type 2 virus (HSV-2) is recovered almost exclusively from the genital tract and is transmitted in the great majority of instances by sexual contact. It has been estimated that approximately 20 to 25 percent of adults in the United States have HSV-2 infection.

Maternal Infection

HSV-2 infections may be divided into three groups: Primary infection indicates no prior antibodies to HSV-1 or HSV-2. Nonprimary first episode defines newly acquired HSV-2 infection with preexisting HSV-1 cross-reacting antibodies. Recurrent infection is reactivation of prior HSV-2 infection in the presence of antibodies to HSV-2.

Only a third of newly acquired primary HSV-2 genital infections are symptomatic. The typical incubation period of 3 to 6 days is followed by a papular eruption with itching or tingling. This eruption then becomes painful and vesicular, with multiple vulvar and perineal lesions that may coalesce (Figure 83-1). Inguinal adenopathy may be severe. Transient systemic influenzalike symptoms are common and are presumably caused by viremia. Occasionally, hepatitis, encephalitis, or pneumonia may develop. In 2 to 4 weeks, all signs and symptoms of infection disappear. Cervical involvement is common and may be inapparent clinically. Some cases are severe enough to require hospitalization.

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FIGURE 83-1 First-episode primary genital herpes simplex virus infection. (From Wendel GD, Cunningham FG: Sexually transmitted diseases in pregnancy. In: Williams Obstetrics. 18th ed. (Suppl 13). Norwalk, CT: Appleton & Lange, August/September 1991.)

In some women, there is partial protection from previously existing HSV-1 antibody (nonprimary first infection). These cases may present as a first clinical infection that does not behave like the primary infection described earlier. In general, these infections are characterized by fewer lesions, less systemic manifestations, less pain, and briefer duration of lesion and viral shedding. In some cases, it may be impossible to differentiate clinically between the two types of first infection.

During the latency period in which viral particles reside in nerve ganglia, reactivation is common. Reactivation is termed recurrent infection and results in herpesvirus shedding. These lesions generally are fewer in number, less tender, and shed virus for shorter periods (2 to 5 days) than those of primary infection. Typically, they recur at the same sites.

Subclinical shedding occurs in at least 60 percent of women with a history of genital herpes infection. It is responsible for many sexually transmitted cases to partners, but the effect on pregnancy has yet to be determined.

Neonatal Infection

Infection is transmitted only rarely across the placenta or intact membranes. The fetus almost always becomes infected by contact with virus shed from the cervix or lower genital tract during birth. Newborn infection has three forms: (1) disseminated, with involvement of major viscera; (2) localized, with involvement confined to the central nervous system, eyes, skin, or mucosa; or (3) asymptomatic.

There is a 50-percent risk of neonatal infection with primary maternal infection, but only zero to 5 percent with recurrent infection. This is thought to be due to a smaller viral load in maternal secretions with recurrent infection. It also likely is related to transplacentally acquired antibody, which decreases the incidence and severity of neonatal disease.

Localized infection is usually associated with a good outcome. Conversely, even when infants are treated with acyclovir, disseminated neonatal infection results in at least a 30-percent mortality rate. Serious ophthalmic and central nervous system damage occurs in 20 to 50 percent of the survivors.

Diagnosis

Tissue culture is optimal for confirmation of clinically apparent infection and asymptomatic recurrences. The sensitivity of culture is nearly 95 percent before the lesions undergo crusting. Cytological examination after alcohol fixation and Papanicolaou staining—the Tzanck smear—has a maximum sensitivity of 70 percent. Use of PCR increases HSV detection by four- to eightfold compared to culture. Serologic assays are available to detect antibody to HSV glycoproteins G1 and G2. They can differentiate between HSV-1 and HSV-2 and permit confirmation of clinical infection as well as identify asymptomatic carriers.

Management

Antiviral therapy with acyclovir, famciclovir, and valacyclovir has been used for treatment of first-episode genital herpes in nonpregnant and pregnant women. Suppressive therapy with these agents has also been used for treatment of recurrent infections and to reduce heterosexual transmission. Oral or parenteral preparations attenuate clinical infection as well as the duration of viral shedding. For intense discomfort, analgesics and topical anesthetics may provide some relief, and severe urinary retention is treated with an indwelling catheter.

Acyclovir or valacyclovir can be used for suppressive therapy during the last month of pregnancy to prevent recurrence near term. Such therapy reduces the signs and symptoms of recurrent infection but does not completely eliminate asymptomatic viral shedding.

According to the American College of Obstetricians and Gynecologists (Management of herpes in pregnancy. Practice Bulletin No. 31, June 2007), cesarean delivery is indicated in women with an active genital lesion or in those with a typical prodrome of an impending outbreak. Thus, cesarean delivery is performed only if primary or recurrent lesions are visualized near the time of labor or when the membranes are ruptured. The recommendation is to disregard the duration of membrane rupture in formulating a plan of delivery for women with perineal lesions.

HUMAN PAPILLOMAVIRUS

Genital papillomavirus infection, either symptomatic or asymptomatic, is common, affecting approximately 30 percent of sexually active women. Several types of human papillomaviruses (HPV) cause mucocutaneous warts or condylomata acuminata. Genital warts are usually caused by HPV types 6 and 11, but may also be caused by intermediate- and high-oncogenic-risk HPV.

Maternal Disease

Genital warts frequently increase in number and size during pregnancy, sometimes filling the vagina or covering the perineum, but rarely making it difficult to perform vaginal delivery or episiotomy. Vulvar lesions often improve rapidly or disappear postpartum.

Neonatal Disease

Viral types 6 and 11 can cause laryngeal papillomatosis (involving the vocal cords) in children, and may have been transmitted by aspiration of infected material at birth.

Management

Because lesions commonly regress after delivery, it is not usually necessary to try to eradicate them during pregnancy. If they produce discomfort, then they are treated. Rarely, surgical debulking the genital warts is necessary in the late second or third trimester.

Trichloroacetic or bichloroacetic acid, 80 to 90 percent, applied topically once a week, is an effective regimen for symptomatic external warts. Internal warts (i.e., those involving the vagina or cervix) are not usually treated. Some clinicians prefer cryotherapy or laser ablation of warts in pregnancy. Podophyllin resin, 5-fluorouracil cream, imiquimod cream, and interferon therapy should not be used in pregnancy because of concerns about maternal and fetal toxicity.

CHANCROID

Haemophilus ducreyi can cause painful nonindurated genital ulcers, termed soft chancres, at times accompanied by painful inguinal lymphadenopathy. Although common in some developing countries, it had become rare in the United States. Drug use and sex-for-drugs are important risk factors. Importantly, the infection is a high-risk cofactor for HIV and syphilis infection.

Diagnosis by culture is difficult because appropriate media is not widely available. Instead, clinical diagnosis is made when typical painful genital ulcer(s) is darkfield negative and herpesvirus tests are negative. Recommended treatment is azithromycin, 1 g orally as a single dose; ceftriaxone, 250 mg in a single intramuscular dose; or erythromycin base, 500 mg orally three times daily for 7 days (CDC, 2010).

TRICHOMONAS INFECTION

Trichomonas vaginalis can be identified in up to 20 percent of pregnant women. Although often asymptomatic, vaginitis manifests with a yellow discharge, abnormal odor, and vulvar pruritus. These women usually have a purulent vaginal discharge, vulvovaginal erythema, and “strawberry cervix.”

Trichomonads are demonstrated readily in a wet mount of vaginal secretions as flagellated, ovoid, motile organisms that are somewhat larger than leukocytes. Trichomonads can also be grown in culture.

Management

Metronidazole is quite effective in eradicating T vaginalis. Oral administration is the preferred route. Metronidazole 2-g orally in a single dose can be used at any stage of pregnancy. The safety of tinidazole in pregnant women has not been well evaluated. All sexual partners should be treated. It is currently recommended that only symptomatic infections be treated.

PREVENTION OF SEXUALLY TRANSMITTED DISEASES IN VICTIMS OF SEXUAL ASSAULT

About 2 percent of victims of sexual assault are pregnant, and most assaults occur before 20 weeks’ gestation. Associated trauma is less common in pregnant women. Shown in Table 83-4 are guidelines for prevention of sexually transmitted diseases in victims of sexual assault.

TABLE 83-4. Guidelines for Prophylaxis of Sexually Transmitted Disease in Victims of Sexual Assault

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For further reading in Williams Obstetrics, 23rd ed.,

see Chapters 59, “Sexually Transmitted Diseases,” and 42, “Critical Care and Trauma.”