Diagnosing and treating STDs in young women

By Carol A. Stamm, MD, and James A. McGregor, MD, CM

The consequences of contracting a sexually transmitted disease can be devastating and long-lasting for adolescent girls. This review of the latest diagnostic testing methods and treatments will help you offer at-risk teens the best of care.

Male and female adolescents who are sexually active face a two-pronged risk. First, they are uniquely susceptible to acquiring common sexually transmittable infections. Second, these infections often have long-term, even lifelong, sequelae, including reproductive impairment (infertility, pelvic inflammatory disease, ectopic pregnancy, and preterm birth), genital neoplasia (cancer of the cervix, vagina, vulva, and penis), recurrent conditions (genital herpes, warts, and pelvic pain in both females and males), and death from ectopic pregnancy or HIV infections. Unfortunately, when an adolescent acquires a sexually transmitted disease (STD), he or she has a 40% risk of acquiring another STD within a year, particularly if gonorrhea is the initial infection.¹ The American College of Obstetricians and Gynecologists recommends annual screening, or as often as the situation warrants, for women at high risk for acquisition of STDs. Sexually active adolescent girls are in this group.

Clearly, pediatricians need to be comfortable diagnosing and treating STDs, the burden of which falls disproportionately on females. The following guidelines, therefore, apply to specific STDs in adolescent women. For more information on the newest diagnostic tests for STDs, see the article "The future is here: Noninvasive diagnosis of STDs".

Trichomoniasis

Five million new cases of trichomoniasis are diagnosed each year.² Trichomoniasis is caused by Trichomonas vaginalis, a flagellated protozoan. Symptomatic female patients with trichomoniasis present with a malodorous yellow or occasionally green vaginal discharge. Many men with the disease are asymptomatic.³ Infection with T vaginalis increases the risk of acquiring HIV infection.⁴

The diagnosis is most often made by identifying motile trichomonads on wet mount preparation. The sensitivity of wet mount examination is only 60% to 80% because a high concentration of the organism is required.⁵ Since the organism loses its motility when it cools to room temperature, one way to improve detection is to leave the specimen swab in a test tube of saline while you are in the exam room and make the slide only when you are ready to use the microscope. Pap smear diagnosis is specific but not sensitive. Diamond's culture, one of two avilable culture media for this organism, is more sensitive than wet mount but more expensive than InPouch TV Culture.^6,7 The InPouch TV Culture uses a clear pouch, which is inoculated and incubated two to five days, then examined under the microscope. In the future, ligase chain reaction (LCR) tests probably will make the diagnosis of trichomoniasis easier and more accurate. These urine-based tests can be self-collected. They are becoming increasingly reliable and are well-accepted by adolescent patients. Compared with culture, LCR tests require less technologist time and expertise and pose less risk of contamination.⁸ Currently, LCR tests are approved by the Food and Drug Administration only for detection of Neisseria gonorrhoeae and Chlamydia trachomatis.

The preferred treatment of trichomoniasis is 2 grams of oral metronidazole, taken all at once. Consumption of alcohol along with this medication can result in a disulfiram-type reaction (nausea and vomiting), so counsel the patient to refrain from drinking while taking metronidazole and for two or three days afterwards. One treatment will cure 90% to 95% of patients. Some individuals may be infected with strains seemingly resistant to metronidazole. Most of these patients respond to higher or prolonged doses of metronidazole, such as 500 mg twice a day for seven days.³ Desensitization has been recommended for patients allergic to metronidazole since this agent is the preferred therapy.⁹ Metronidazole gel is less efficacious than the oral form and is not recommended.

Sexual partners of individuals with trichomoniasis require treatment. As with all STDs, patients should avoid sexual intercourse until both partners have taken the appropriate medication and are free of symptoms. Pregnant adolescents should be treated promptly. The dosage of metronidazole is the same for patients who are pregnant and those who are not. Many providers prefer to treat after embryogenesis is complete (after 12 weeks of gestation).

Chlamydia

Infection with C trachomatis is most common in adolescence. The prevalence of Chlamydia in adolescent populations ranges from 6% to 12%, making routine screening essential and cost-effective for sexually active teenagers.¹⁰ The Centers for Disease Control and Prevention recommend such screening during routine pelvic examination.³ Unfortunately, as many as 80% of infections are asymptomatic.¹¹ When symptoms are present, mucopurulent cervicitis and urethral infection are the most common.¹² Being younger than 25 is the most consistent and powerful risk factor for chlamydial infection. Patients under 25 years of age should be offered routine testing, as should individuals who have had more than two sexual partners in the last 12 months. In general, history is inaccurate and unhelpful.¹⁰ Indeed, a recent study demonstrated that predictors of infection such as the reason for the clinic visit, prior infection with Chlamydia, or multiple or new partners fail to identify the group of adolescents with most of the infections.¹³ Similar to other infections (HIV and HBV), testing is best offered nonselectively to all individuals at risk.

A recent prospective study in the managed care population demonstrated that screening of asymptomatic young women (younger than 24) leads to treatment and decreases the risk of pelvic inflammatory disease.¹⁴ A similar study with female army recruits showed that screening by age provides cost-savings.¹⁵ Routine screening is particularly important when the prevalence rate of chlamydial infection is 6% or greater.¹⁶ Some investigators have recommended screening sexually active adolescents every six months.¹⁷ We suggest that adolescents be screened opportunistically at medical care visits and before or after contact with a new partner.

The imperative for more frequent screening may enhance the importance of urine screening, which is ideal for adolescents who decline pelvic examination.¹⁸ Diagnosis is optimized by use of DNA amplification techniques, preferably LCR as it has a higher sensitivity than polymerase chain reaction (PCR).¹⁹ These techniques improve the sensitivity of the diagnosis. The specificity is nearly 100%. These tests also are efficacious when performed on urethral or cervical specimens. The LCR sensitivity and specificity with respect to cervical culture are approximately 88.6% and 99.7%, respectively.¹⁰ Amplification tests offer similar performance parameters for self-collected vaginal or urine samples.

The LCR and PCR technology is so good that it should be considered the best way to establish the diagnosis. The commonly offered enzyme immunoassay (EIA) is less sensitive . EIA tests require Dacron swabs instead of cotton to collect urethral specimens from females and males or cervical specimens from females. Take care to wipe the cervix free of mucus to improve the microbial antigen recovery. Also be careful not to let the swab touch the vaginal side-wall since some gram-negative bacteria can yield false-positive results.²⁰ Unfortunately, EIA testing misses approximately 40% of infected patients.²¹

The goals of treatment are threefold: to eliminate symptoms, risks of complications, and disease transmission. Infectious sequelae for C trachomatis infection include pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic pelvic pain. It is important to provide cotreatment for gonorrhea since acquisition of both infections is common.

To ensure compliance in adolescents, we prescribe the easiest treatment regimens possible for both nonpregnant and pregnant women and their partners. In a study in pregnant women, single-dose azithromycin was found to improve compliance and decrease the risk of a repeat positive culture.²² The cost of a dose ranges from $15 to $30. Single-dose therapy also offers the opportunity for directly observing patient compliance.²⁰ Azithromycin has been found to be more cost effective than doxycycline therapy for young women with uncomplicated cervical chlamydial infection.²³ It is prudent to offer a test of cure to identify treatment failures, noncompliance, and reinfections. Counsel the adolescent to avoid intercourse for seven days following single-dose therapy or until a seven-day treatment course has been completed.³

Asymptomatic individuals serve as a reservoir for spreading disease. Anyone with whom the infected patient has had sexual contact within 60 days before symptoms began or the diagnosis was made must be evaluated and treated. If the last contact occurred within more than 60 days, that contact should be treated.³ Table 1 summarizes recommended treatments.

TABLE 1
Treatment of adolescents with Chlamydia infection*

Erythromycin base 500 mg qid for 7 days

Erythromycin ethylsuccinate 800 mg qid for 7 days

Ofloxacin 300 mg bid for 7 days

Gonococcal infection

Although N gonorrhoeae infection is declining, 600,000 individuals in the United States are newly infected with this organism each year. The rate of gonorrhea in the US is highest in females 15 to 19 years of age.³ As many as 80% of young women infected with gonococcal infection are asymptomatic.¹² Symptoms, which include increased vaginal discharge, dysuria, and pelvic discomfort or pain, may not be apparent until the young woman is already subject to such complications as infertility from tubal injury, increased risk of ectopic pregnancy, and chronic pelvic pain. Many sites can be infected, including the cervix, urethra, rectum, and pharynx. If the infection ascends from the cervix, it may cause salpingitis (inflammation of the uterine tube) or pelvic inflammatory disease.

A positive culture or demonstration of gram-negative intracellular diplococci in secretions makes the diagnosis. Gram stains may be slightly less reliable in women than in men. The LCR and PCR technology offers improved sensitivity and should be used, if available.

As many as 50% of patients infected with gonorrhea are co-infected with Chlamydia, so selecting antibiotic coverage suitable for both organisms is reasonable.³ Reports of quinolone-resistant N gonorrhea infections are increasing; obtaining culture and sensitivity testing for patients with treatment failures will help to identify these infections. An alternative is to treat every patient who has gonorrhea with two agents.³

Table 2 lists recommended treatments. In the adolescent patient, simple treatment regimens optimize compliance. One gram of azithromycin will treat most cases of chlamydial infection and about 93% of cases of uncomplicated gonococcal infection. Two grams of azithromycin treat most gonococcal infections, but gastrointestinal side effects limit patients' ability to tolerate this higher dosage.³ Sexual contacts should be treated as they are for chlamydial infections.

TABLE 2
Recommended treatments for gonococcal infection

Genital herpes simplex virus infection

About 45 million people in the US are afflicted with this sexually transmitted infection.³ As many as two-thirds of affected individuals are unaware of their diagnosis, however. These individuals create an asymptomatic reservoir of infection. About 12% of adolescents have antibodies to HSV-2, indicating prior infection,²⁴ although the actual number may be higher since many infections are unrecognized. One-third of patients infected with herpes have dull pain or itching and small lesions or pimples in the vulva. Healing takes two to four weeks. Subsequent outbreaks usually last five to 10 days and occur four to five times a year. Triggers for recurrent episodes include stress, menses, trauma, and other illnesses. Recurrence may be asymptomatic or less painful than the original episode. Some primary outbreaks go completely without notice, however. Risk factors for disease acquisition include not using barrier contraceptives (condoms) and having more than one sexual partner. The risk of acquisition with one partner is less than 10% but may be as high as 40% with more than two partners.²⁵

Diagnosis of genital herpes rests primarily on recognition of typical fluid-filled blisters on an erythematous base ("dew drops on a rose petal") or, more commonly, atypical lesions (painful papules and ulcers). Viral culture or antigen detection confirms the diagnosis. Serologic diagnosis using glycoprotein antibody or Western blot analysis will become an effective means of confirming the clinical diagnosis, but these tests are not yet widely available. Development of protective antibodies to HSV typically takes four to six weeks.²⁶ Partners could be tested with an HSV-2 antibody assay to detect concordance or discordance. Since the virus can be contagious even after lesions have healed, consistent use of barrier contraceptive methods is recommended, though it may not be completely protective. Prevention of transmission to uninfected seronegative partners remains problematic.

Treatment is aimed directly at relief of symptoms and reduction of viral shedding but will not provide permanent cure. Many studies support the efficacy of acyclovir 200 mg taken orally five times a day; 400 mg three times a day is also effective. Alternatively, valacyclovir and famciclovir can be taken twice and three times a day, respectively. Table 3 shows treatment regimens.

TABLE 3
Treatment of genital herpes simplex virus infection

All three drugs appear to be effective in suppressing recurrent herpetic outbreaks.²⁷ Patients receiving suppression therapy may still transmit the disease, however.²⁸ It is unclear if condoms protect against herpes transmission. It seems prudent to encourage patients to abstain from intercourse during outbreaks and always to use condoms, which may protect against asymptomatic shedding at other times. In some patients, zinc and vitamins A and C supplementation may decrease recurrences, but good studies to support such supplementation are lacking. Ultimately, vaccination may be the most effective strategy for dealing with this STD.

Syphilis

Syphilis has become rare in North America. Testing for HIV should be offered to patients with syphilis, since about 10% to 15% will be concomitantly infected.²⁹ Eradication of syphilis has become possible if screening and treatment of at-risk populations is intensified.

Primary syphilis may present as an initial painless chancre, which is highly infectious and often is not perceived by the patient. During the secondary stage, which is also extremely contagious, many patients have fever, lymphadenopathy, and, most commonly, a macular rash over the palms and soles. No symptoms are apparent during the latent stage. Tertiary stage disease may include neurologic, cardiac, vascular, or ophthalmic symptoms. Left untreated, syphilis during pregnancy may cause congenital syphilis, preterm labor, stillbirth, or neonatal death.

Diagnosis depends on serologic screening and rescreening of high-risk patients. Dark-field microscopy with identification of the spirochetes is the definitive method of making the diagnosis in patients with chancre. Serologic tests include the non-treponemal Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test. If the diagnosis is made with one of these serologic tests, a confirmatory fluorescent treponemal antibody absorption test (FTA-ABS) is required because diseases such as systemic lupus erythematosis and many viral infections can cause a false-positive result. Patients should not be diagnosed without an FTA-ABS or other similarly accurate confirmatory test.

Most patients will have nonreactive nontreponemal serologic tests after adequate treatment; some patients will have persistent titers, however, and are considered to be sero-fast.³ Reactive treponemal tests remain permanently reactive in most patients after treatment.³ Patients with AIDS may fail to seroconvert and should be treated presumptively in the presence of symptoms. A patient may be considered cured when symptoms resolve with at least a fourfold decline (two-dilution) of the nontreponemal test titer over four months.³⁰

The treatment of choice for primary and secondary syphilis is long-acting parenteral penicillin G. It produces complete cure, evidence collected over four decades shows.³ Penicillin is the only therapy with proven efficacy in treating neurosyphilis.³ Pregnant patients and those with neurosyphilis who have penicillin allergy should undergo desensitization and treatment with parenteral penicillin G. Some evidence suggests that congenital syphilis is more likely with secondary syphilis than with primary or tertiary stage disease.³⁰ This may be due to heavier spirochetemia, which may cause placental and fetal infection. Secondary stage disease is a marker for a higher probability of fetal infection.³¹ Table 4 lists recommended treatments for syphilis.

TABLE 4
Treatment of adolescents with syphilis

After treatment, follow-up titers at three, six, and 12 months are recommended. Consider treatment failure or re-infection if the patient has persistent signs or symptoms or if the fourfold increase in the nontreponemal test titer noted at diagnosis does not decrease after therapy.³ About 5% of treated patients experience treatment failure, so proper follow-up is essential.³¹ It is prudent to evaluate these patients for HIV infection. Retreatment consists of three weekly intramuscular injections of benzathine penicillin G 2.4 million units. In general, serologic testing at six and 12 months will help assess adequacy of treatment in patients who are not infected with HIV. HIV-positive patients should have serologic testing for the first time at three months after treatment.³

Treatment of sexual partners is mandatory. Most states require the reporting of all persons infected with syphilis. General guidelines for a patient with primary syphilis call for contacting sexual partners for the three months prior to diagnosis plus the period during which symptoms were present. For a patient with secondary syphilis, contact sexual partners for the last six months plus the duration of the symptoms. For a patient with early latent syphilis, sexual partners for the last year should be contacted.³

Promoting prevention

Caring for adolescent patients provides many opportunities for providing primary and secondary STD prevention strategies. By identifying young women at risk for STDs, we can provide counsel, barrier protection, and a reliable method of contraception. In this way, we can reduce unintended pregnancy and sexually transmissible infections. Promoting abstinence certainly has a role in preventing STDs. Abstinence will not be the primary method of prevention for many adolescents, however.

Remember to screen for Chlamydia at routine examinations. When a young woman has a sexually transmitted infection, offer her treatment with single-dose therapy whenever possible. In the future, topical microbicides and vaccinations may also be part of the strategy to prevent STDs and their devastating sequelae.

REFERENCES

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15. Howell MR, Gaydos JC, McKee KT, et al: Control of Chlamydia trachomatis infections in female army recruits: Cost-effective screening and treatment in training cohorts to prevent pelvic inflammatory disease. Sex Transm Dis 1999;25:519

16. Genc M, Mardh PA: A cost-effectiveness analysis of screening and treatment for Chlamydia trachomatis infection in asymptomatic women. Ann Intern Med 1996;124:1

17. Orr DP: Screening adolescents for sexually transmitted infections. JAMA 1998;280:564

18. Lappa S, Moscicki AB: The pediatrician and the sexually active adolescent: A primer for sexually transmitted diseases. Pediatr Clin North Am 1997;44:1405

19. Schachter J, Stamm W, Quinn T: Ligase chain reaction to detect Chlamydia trachomatis infection of the cervix. J Clin Microbiol 1994;32:2540

20. Binkley S, McGregor JA: The new paradigm for the prevention and management of pelvic inflammatory disease and common bacterial STDs in women and their partners: Using nucleic acid amplification and single-dose regimens. The Journal of Clinical Practice in Sexuality 1995;10:5

21. Woods G: Update on laboratory diagnosis of sexually transmitted diseases. Clinical Laboratory Medicine 1995; 15:665

22. Wehbeh HA, Mary RR, Shahem S, et al: Single-dose azithromycin for Chlamydia in pregnant women. J Reprod Med 1998;43:509

23. Magid D, Douglas JM Jr, Schwartz JS: Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections: An incremental cost-effectiveness analysis. Ann Intern Med 1996; 124:389

24. Rosenthal SL, Stanberry LR, Biro FM, et al: Seroprevalence of herpes simplex types 1 and 2 and cytomegalovirus in adolescents. Clin Infect Dis 1997;24:135

25. Annunziato PW, Gershon A: Herpes simplex virus infections. Pediatr Rev 1996;17:415

26. Brown ZA, Selke S, Zeh J et al: The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997;337:509

27. Diaz-Mitoma F, Sibbald R, Shafran SD, et al: Oral famciclovir for the suppression of recurrent genital herpes. JAMA 1998;280:887

28. Engel JA: Long-term suppression of genital herpes JAMA 1998;280:928

29. Sung L, MacDonald WE: Syphilis: A pediatric perspective. Pediatr Rev 1998;19:17

30. Alexander JM, Sheffield JS, Sanchez PJ, et al: Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999;93:5

31. Rolfs RT: Treatment of syphilis, 1993. Clin Infect Dis 1995;20(Suppl):S23

DR. STAMM is Assistant Professor of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver Health Medical Center, Denver, CO.

DR. McGREGOR is Professor of Obstetrics and Gynecology at the same institution.

 

James McGregor, Carol Stamm. Diagnosing and treating STDs in young women. Contemporary Pediatrics 2001;2:53.