SEXUALLY TRANSMITTED INFECTIONS
Judith Absalon, M.D.
Sexually transmitted infections (STIs) are a common medical problem throughout the world. They affect men and women across a wide range of ages and socioeconomic classes and are a topic of discomfort for many patients as well as clinicians. For many, sexually transmitted diseases continue to carry an associated stigma and are felt to be a "private" matter. As a result these vastly curable diseases persist in epidemic numbers.
The STIs are a group of more than 25 organisms and a variety of clinical syndromes that lead to significant morbidity and mortality. Nearly all STIs have been shown to increase the risk of HIV. There are more than 15 million new STIs in the U.S. each year; of the top ten most common infectious diseases reported to the Centers for Disease Control and Prevention (CDC) in 1995, five were sexually transmitted. In addition, many STIs are asymptomatic and STI rates may be vastly underestimated.
While the incidence of some STIs such as gonorrhea and early syphilis has steadily declined in the U.S. for the past ten to twenty years, rates of new infection have increased dramatically for others (chlamydia, HIV, herpes, HPV). The United States continues to have overall rates of STIs at least double those in other resource-rich countries such as England, Sweden, Germany, and Canada.
Routine discussion of sexual history, behavior and risk, as well as a thorough genital examination are essential components of ambulatory medicine. Providers must also be able to counsel patients about safer sex and risk reduction. This chapter will familiarize you with the clinical (diagnosis, symptoms and treatment) aspects of the major sexually transmitted disease syndromes; I have also included a section on the sexual history. A chart of treatment guidelines for the major syndromes is provided at the end of the chapter (Appendix A). The NYC Department of Health website is an additional resource (www.ci.nyc.ny.us/health), as is the CDC’s Division of STD Prevention, website (www.cdc.gov/nchstp/dstd/dstdp.html). HIV will be discussed in Chapter 21.
The Sexual History
A thorough sexual history should always be taken as part of your routine general medical evaluation. This includes patients of all age groups – it is an error to assume that patients beyond a certain age are not sexually active. Because of the sensitivity of the topic many patients will not volunteer the information, and the provider must ask specific closed-ended questions. In addition, it is essential to remember that different people have different sexual practices. For example, do not assume that a female patient has male partners or that she does not have both male and female partners. The fact that a patient is married does not automatically imply that s/he only has sex with one person. Using the term "sexual partner" is a good way to avoid labels ("boyfriend" "wife") that may make some patients uneasy. The most important factor in this process is to make the patient feel comfortable. Questions that allow room for a range of responses are best, as is "cultivating a listening stance." Do not suggest answers ("you don’t have any sexual problems, do you?"), interrupt patients, or signal discomfort with the topic. Use language that is specific and clear. Finally, asking and accepting a patient’s responses without any moral judgment will enable an ongoing relationship and hopefully permit patients to present with concerns about their sexual health at subsequent visits.
Some examples of important questions include:
In women a brief gynecologic history should be obtained:
Prevention and Safer Sex
After discussing the sexual history, primary care providers should counsel all patients about avoiding sexually transmitted diseases. Counseling guidelines are available from the CDC, and are discussed at greater length in Chapter 20. As with all risk-reduction education, respectful, non-judgmental and patient-specific instructions are best. The most effective way to prevent sexually transmitted infections is to abstain from penetrative sexual intercourse with infected partners, and all STD-prevention counseling should include information about abstinence. If patients choose to be sexually active, they should be informed that correct and consistent use of latex barrier protection could reduce their chance of acquiring a sexually transmitted disease. Male condoms and the female (RealityTM) condom effectively reduce the risk of STD infection (including HIV). Vaginal spermicides can reduce the risk of cervical gonorrhea and chlamydia, but are not protective against HIV or for men.
A complete examination to assess the presence of sexually transmitted disease should include careful examination of the genitalia, as well as the skin, including palms and soles. In addition, many manifestations of STDs include abnormalities in the anus and inguinal lymph nodes; these areas must be carefully examined.
Genital herpes is a common disease whose prevalence has increased steadily since the 1960’s. It is a recurrent, incurable viral infection, affecting over 45 million people in the United States alone. Most cases of genital herpes are caused by herpes simplex virus type 2 (HSV2), but as much as 30 percent of genital herpes infections are due to HSV1.
"Classic" symptoms are divided into the symptoms of primary infection and those of recurrent infection. In primary infection (the first episode of genital herpes in a patient who has never been infected with HSV1 or HSV2), 95 to 99 percent of patients have multiple, bilateral painful ulcers on an erythematous base, which start as papules or vesicles and spread. The ulcers heal after two to three weeks. Patients often have prolonged systemic symptoms: fever, pharyngitis, myalgia, headache, malaise, tender lymphadenopathy, and cervicitis. The latter is seen in 70 to 90 percent of women. Patients whose first episode of genital herpes has been preceded by oral HSV1 infection may have a milder clinical course of first episode genital herpes.
Recurrent genital herpes is characterized by symptoms that are localized to the genitalia, unilateral lesions and a smaller area of involvement. Symptom duration is shorter – usually less than two weeks – and 90 percent of patients have prodromal symptoms. Patients may have more typical ulcerations or "atypical" genital herpes during recurrent episodes. "Atypical herpes is actually very common – patients have small linear ulcerations rather than the classic ulcer; these can be mistake for scratches or cuts. A proportion of patients can also have subclinical or asymptomatic viral shedding of the virus, when no genital lesions are clinically apparent. Asymptomatic shedding is highest during the first 6 months after primary infection. Immunocompromised patients, such as those with HIV, can have a prolonged clinical course and more frequent recurrences.
Genital herpes can cause serious complications such as bacterial superinfection, extragenital lesions, dissemination, aseptic meningitis, transverse myelitis and sacral radiculopathy. PID is rare.
The painful ulcers of genital herpes are so characteristic of the disease that it is most often diagnosed clinically. Other modalities include the Tzanck smear, which is highly sensitive and specific but must be performed within hours of collection. Viral culture is also an accurate tool, but sensitivity decreases as the lesions age. Serologic studies are rarely clinically useful, since they do not distinguish between current and prior HSV infection. Serology may helpful to document first episode infections. We recommend viral culture if the patient presents within the first two to three days of symptoms; the culture media (and viral culture request forms) are available from the nursing staff.
Treatment and Partner Management:
There is no curative therapy for genital herpes. In immunocompetent patients with primary genital HSV, treatment with acyclovir, famciclovir or valacyclovir increases the rate of healing but does not prevent recurrences. The use of valacyclovir permits once-daily dosing with similar effectiveness to prior regimens. Recurrences ("flares") can be treated to speed resolution of symptoms; treatment can be effectively patient self-initiated in selected populations. Patients with frequent (4-12) episodes of genital herpes each year or who have significant psychological distress during recurrences may consider chronic suppressive therapy (see Appendix A). Partners are not routinely evaluated by the Department of Health, but should be notified of their exposure risk. It is important to inform patients that transmission occurs both in the presence of lesions and two to three days prior to the eruption.
Human papillomavirus (HPV) includes over 100 genotypes of HPV – more than 35 of which infect the genitalia. HPV infection is a highly prevalent disease and it is likely that 20 to 40 percent of sexually active adults are HPV-positive. Data on the incidence of disease are difficult to obtain because many patients are asymptomatic, do not seek therapy (genital warts), or have had infection for an undetermined length of time when they present for evaluation (cervical, anorectal cancer), however HPV is likely the most common STI. Some authors estimate that visible genital warts are present in one percent of sexually active American adults. Prevalence is highest in sexually active young adults (18-28 years).
Symptoms are often absent or unrecognized. The most common manifestations are genital warts, which occur most commonly on the penis, scrotum, urethral meatus, introitus, vulva, perineum and perianal areas. Genital warts are most commonly caused by HPV types 6 and 11. The examiner may see:
Certain types of HPV infection (HPV types 16, 18, 31, 33, 35) can lead to transformation of the cervical squamocolumnar junction in women known as squamous intraepithelial lesions (SIL), a precursor to cervical cancer. Persistent HPV infection is a known risk factor for cervical cancer, and a recent study demonstrated an increased risk of cervical cancer after a single HPV-positive test. Screening with Papanicolau smears and treatment of early cervical cancer has been shown to have a dramatic impact on mortality (see Chapter 1).
Like genital herpes, the characteristic lesions of genital HPV are often diagnosed clinically. Screening for subclinical HPV infection itself is not currently recommended, although Pap smear screening for early cervical cancer is, as mentioned, a standard of care. Some guidelines also recommend anal Pap smears for HIV-infected men who have sex with men. As PCR technology is standardized, screening for specific oncogenic strains of HPV may become more common.
Treatment and Partner Management:
The treatment of genital warts usually consists of topical therapy (see Appendix A). A follow-up examination (for genital warts) is not necessary once treated unless symptoms persist and alternative therapies need to be considered. Partners are not routinely examined by the Department of Health, but should be notified of their exposure; Pap smear screening of all female partners is recommended.
Syphilis is a systemic disease caused by the bacterium Treponema pallidum, spread through sexual contact with an infected source and manifesting as a series of clinical and sub-clinical stages. Syphilis is currently at an all-time low in the United States. The most recent available data suggest that the incidence of primary, secondary and early latent syphilis rates in NYC is less than one case per 100,000. Rates of early syphilis however are markedly higher in certain areas of the Southern United States; rates are also comparatively high in Newark, N.J. and Washington, D.C. In October of 1999, the CDC launched a national plan to eliminate syphilis in the US. While the disease will not be eradicated, this is an effort to drive new cases of early syphilis in all parts of the US to a very low level and to markedly decrease transmission of early infection.
As with other diseases of long duration and potential latency, a definitive diagnosis is sometimes difficult to make and outcomes assessment is problematic. Thus, standards for diagnosis and treatment are based on scarce data and are influenced by syphilis’ sensational role in history. These cases of advanced disease, which were common in the pre-penicillin era, rarely occur today, even in the HIV-infected population.
Syphilis is characterized by finite periods of illness, spontaneous remission, and relapse. The diagnosis, therefore, may not be readily apparent from the patient’s history and physical exam.
Primary syphilis: After exposure to an infected source (someone with primary or secondary syphilis), a painless, papule appears at the site of inoculation. The average incubation period is three weeks, but can range from two to six weeks. The papule grows into an indurated painless ulcer (a chancre) with a clear base and with no exudate. While single ulcers are classic, multiple syphilitic chancres can frequently occur. Bilateral regional lymphadenopathy is present in the majority of patients. Without treatment the chancre will heal spontaneously in three to six weeks. Remember - a syphilitic chancre can occur at any site! After resolution of the primary chancre, 50 percent of patients will enter a latent phase; the remaining 50 percent have a secondary illness.
Secondary syphilis: This is the disseminated stage of syphilis and can occur immediately following the chancre, at the same time as the primary stage, or as long as six months later. Manifestations include fever, malaise, headache, generalized lymphadenopathy, a generalized rash (classically papular, discrete, scaly) with involvement of the palms and soles, mucous patches in the oral or genital regions, wart like growths in moist intertringinous regions (condyloma lata), and alopecia. This stage resolves in 3 – 12 weeks. There may be recurrence of the secondary stage in 25 percent of untreated patients.
Latent syphilis: Latent syphilis is the period of infection when patients are seroreactive for syphilis but are without clinical symptoms or signs. Patients who have acquired syphilis within one year are classified as having early latent syphilis. These patients continue to be at risk for recurrent secondary disease. Patients who have had syphilis for more than a year are classified as having late latent syphilis, and are not at risk for recurrence. In the absence of recent sexual contact with a known infected partner or recent negative RPR, most patients diagnosed with syphilis on the basis of serology are presumed to have late latent disease. The distinction between early and late latent disease is important; both require treatment, but the treatment regimens are different (a single IM injection of 2.4 million units benzathine penicillin G is sufficient for early latent syphilis, while late latent disease is treated with three IM doses delivered at weekly intervals).
Tertiary syphilis: This stage occurs in up to one-third of untreated patients and can occur from months to decades after the primary infection. Tertiary syphilis can involve multiple organ systems: CNS (asymptomatic, meningeal involvement, cerebrovascular involvement, parenchymatous, gummatous); cardiovascular (aortic aneurysm, coronary artery disease, aortic valve disease, myocardial gummas); musculoskelatal (gummas of skin, bones, and mucous membranes such as the esophagus, tongue and mouth). Aortitis and other cardiovascular lesions appear 10 to 15 years after infection. The overall risk of late CNS infection in an untreated patient is four to nine percent and can occur after five to 30 years.
Neurosyphilis: This includes any patient with evidence of neurologic involvement and can occur during any stage of syphilis. HIV-infected patients may show evidence of neurosyphilis very early in their course and most experts recommend lumbar puncture for all HIV-positive patients with untreated latent disease.
There are several laboratory techniques that can indicate the presence of syphilis infection. The positive predictive value for each test may vary geographically due to variation in the prevalence of the disease.
This method is used to identify organisms when a primary or secondary lesion is present using a microscope with an inverted condenser which allows the small organism to be viewed over a dark background. Any suspicious lesion should be sampled for DF, if possible, as this is the diagnostic test of choice in primary syphilis. It is exquisitely sensitive and specific, but access to darkfield microscopy at CPMC is limited.
Serologic assessment is the most common way of detecting infection with syphilis, but is limited due to difficulty in determining sensitivity and specificity of these tests – no gold standard exists.
Nontreponemal tests: RPR , VDRL
These are non-specific assays that test for a common mammalian protein (cardiolipin) on the Treponema organism. This protein is also present in other diseases and non-diseased states and can result in positive tests in a patient without syphilis (SLE, anti- cardiolipin syndrome, pregnancy, HIV and aging). Sensitivity of the VDRL test is estimated to be 68 percent, 99 percent and 70 percent for untreated primary, secondary, and tertiary syphilis respectively. Specificity is about 99 percent in healthy non-pregnant adults and 84 percent in those who are sick.
These RPR and VDRL are used for screening and require a confirmatory test for the diagnosis. They are quantitatively performed; in the absence of treatment, titers rise sharply in the first year of infection and taper to a low level by year five. Titers respond predictably to therapy, and are usually used to monitor treatment. Non-treponemal tests may be negative in primary syphilis if the lesion is seen early. The RPR is more commonly used in the US because many samples can be run simultaneously and the test is easier to perform than the VDRL. One third of patients may revert to a negative non-treponemal test after adequate treatment for syphilis.
Treponemal tests: MHA-TP (TPHA), FTA-ABS
The Fluorescent Treponemal Antibody Absorption test (FTA-ABS) and the Micro-hemagglutinin Treponema pallidum (MHA-TP) assays are specific tests for T. pallidum and measure surface antibody to a laboratory synthesized (non-virulent) form of T. pallidum. MHA-TP is a hemagglutination test and FTA-ABS is a fluorescent labeled antigen-antibody complex identification method. Once reactive, these tests remain positive for life. They are qualitative tests only; MHA-TP is easier and less expensive. The sensitivity of the FTA-ABS in primary, secondary, and symptomatic late syphilis is 90 percent, 100 percent and 100 percent, respectively. Its specificity is no better than that of the VDRL, contrary to widespread belief. False-positive tests can occur in persons with autoimmune and connective tissue disorders as well as in those with genital herpes.
Treatment and Partner Management:
The treatment of syphilis is outlined in Appendix A. An adequately treated patient is one in whom the RPR titer decreases by two serum dilutions (or fourfold) over six to twelve months. Patients should be evaluated clinically and serologically at six months and 12 months for response. Patients who have a two serum dilution (fourfold) increase in titer have failed treatment or were re-infected (less common) and should be retreated after evaluation for HIV infection. All partners of persons with syphilis should be notified and evaluated serologically and clinically for disease. Recent (within three months) sexual partners of patients with primary, secondary or early latent syphilis should be treated empirically for primary syphilis. Screening for syphilis is also recommended for certain asymptomatic groups, including pregnant women, patients with HIV infection, and injection drug users; the prevalence of syphilis in the two latter groups is greater than 20 percent. Routine screening of hospitalized patients is not recommended, due to the reduced specificity of screening tests in patients with other illnesses.
Gonorrhea, caused by Neisseria gonorrhea, is a sexually transmitted infection of the columnar or cuboidal noncornified epithelial cells of mucous membranes. Accurate data on incidence of gonorrhea worldwide is difficult as most countries have poor reporting systems for gonorrhea. There are over 600,000 new infections of gonorrhea per year in the United States. While this incidence of this STI has had declined over the past forty years, it is still much more common in the US than in other developed countries. Gonorrhea is most prevalent in 15 – 29 year olds. Women are much more likely to have asymptomatic infections. The highest rates of infection occur in late summer and there is an increased association in people with lower socioeconomic status and higher level of sexual activity.
Multiple clinical manifestations are associated with gonoccocal infection including:
Gonorrhea can be diagnosed via culture or by non-culture mechanisms. A urethral or cervical specimen cultured on modified Thayer Martin culture medium has an 80 to 95 percent sensitivity and is highly specific. Non-culture mechanisms include DNA hydridization, using a single stranded DNA probe to hybridize to N. gonorrhea rRNA; this has a sensitivity of 89-97 percent and a specificity of 99 percent. Nucleic acid amplification – LCR, PCR – is highly sensitive and specific and can be used on urine samples.
Treatment and Partner Management:
Once treated, neither disease-specific follow-up nor test of cure is required. All partners with sexual contact within the previous 60 days must be contacted and treated empirically for gonorrhea and chlamydia, as many patients are co-infected. In cases where the last sexual encounter was longer than the prior 60 days, the last known sexual partner should be tested and treated if positive. While N. gonorrhea is relatively resistant to penicillins and tetracyclines, there is low occurrence of quinolone resistance in the United States. In those who have recently visited Asia, quinolone resistant N. gonorrhea should be considered.
Sexually transmitted infections caused by Chlamydia trachomatis are currently the most common bacterial sexually transmitted disease in the United States. New York City had the 6th highest reported case rate in the nation in 1999. Annual rates of infection have been estimated anywhere from four to five million cases across the nation, with a large percentage of these infections in both men and women being asymptomatic. Prevalence data is variable, however published data have given estimates from 5 percent to 24 percent, depending on the population studied.,, In 1995, the cost of treating chlamydial infections were estimated at $2.4 billion.
Clinical symptoms are very similar to gonnoccal infections. They include:
Until recently, cell culture has been the gold standard for the diagnosis of C. trachomatis. Because of the technical difficulties – and difficulties with transport – cell culture is being replaced with non-culture techniques. At present, DNA amplification methods (PCR, LCR) are more sensitive, detecting 15 to 40 percent more infected persons than cell culture; these techniques are rapidly replacing culture as the gold standard and tests of choice. Antigen detection, such as DNA hybridization, EIA/ELISA, and DFA (direct fluorescent antibody test) are rapid and accessible; serologic testing, in contrast, is rarely used.
Treatment and Partner Management:
Because of the high efficacy of current treatment for chlamydial infection, test of cure is not required. All sexually partners within 60 days of infection should be evaluated and treated empirically. In cases where the last sexual encounter was longer than 60 days, the last known sexual partner should be treated.
Trichomoniasis is caused by infection with the protozoa Trichomonas vaginalis, which is transmitted primarily through sexual contact. Worldwide, it infects over 200 million people annually. In the United States the annual incidence of trichomonas infection has decreased steadily since 1975, however in certain populations, prevalence of this STD can be quite high (i.e. up to 60 percent of female prison inmates and commercial sex workers).
Women typically present with vaginitis (a yellow-green, foul-smelling discharge) associated with an edematous and/or excoriated vulva. The vagina and cervix may be erythematous and inflamed in some, but 20 to 50 percent of infected women may not report symptoms. Men typically present with NGU or may be asymptomatic. In general, men are treated empirically when known to have an infected contact or in cases where they have not responded to anti-chlamydial treatment after a diagnosis of NGU.
A wet mount preparation of vaginal or urethral secretions to identify motile trichomonads is the most common diagnostic tool; a microscope and wet-mount preparation materials are available in AIM 15. Culture remains the gold standard diagnostic test (multiple culture media are commercially available, all with variable sensitivities). Pap smears can sometimes report the presence of trichomonads, however these results are unreliable as white blood cells can be confused with the organism. In our setting, cultures are universally performed at the time of Pap testing to avoid this confusion.
Treatment and Partner Management:
Disease-specific follow-up is unnecessary but sex partners within the 60 days preceding symptom onset should be treated empirically.
Pelvic Inflammatory Disease (PID)
Pelvic inflammatory disease (PID) is an inflammatory disorder of the female upper genital tract. It involves any combination of endometritis, salpingitis, tubo-ovarian abscess and pelvic peritonitis. While it is most often caused by infection with C. trachomatis and N. gonorrhea, "nonpathogenic organisms" (anaerobes, G. vaginalis, H.influenza, Streptococcus agalactiae) can also lead to PID. Because accurate diagnostic criteria do not exist, the true incidence and prevalence of the disease is lacking.
Symptoms vary and range from very mild to severe (abdominal pain, fever, vaginal discharge, dysuria, vomiting, anorectal symptoms). It is important to determine whether the patient requires parenteral therapy and inpatient monitoring; inability to take oral medicine or severe dehydration are clear indications for hospitalization. Patients who have a high likelihood of noncompliance should be considered for inpatient therapy. All patients with PID should be followed very closely – if outpatient therapy is chosen, the patient should be seen back within three days.
The diagnostic gold standard for PID is laparoscopy, but this is frequently unavailable in acute cases and rarely indicated in milder cases. Diagnosis is usually made on clinical grounds. Treatment is indicated when all of the following are present in a sexually active woman (minimal criteria): lower abdominal pain, adnexal tenderness and cervical motion tenderness. Fever, high ESR, C-reactive protein, and evidence of C. trachomatis or N. gonorrhea infection are additional supportive criteria. The presence of endometritis on biopsy, thickened fluid filled tubes, tubo-ovarian abscess or abnormal laparoscopic findings are definitive criteria for PID.
Treatment and Partner Management:
Oral regimens are described in Appendix A. As noted, if oral regimens are chosen, the patient should be re-evaluated for improved symptoms within three days. If the symptoms have not improved, hospitalization for intravenous therapy, gynecologic consultation, further diagnostic testing or surgical intervention should be strongly considered. All sex partners who have had sexual contact within the preceding 60 days should be evaluated and treated empirically for chlamydia and gonorrhea.
Non Gonoccocal Urethritis
The presence of urethral inflammation manifested by urethral discharge, dysuria or itching or the presence of >4 polymorphonuclear cells on high power field microscopy are identified on a Gram–stained urethral smear defines non-gonococcal urethritis (NGU). While many cases of NGU are secondary to Chlamydia trachomatis, other organisms, such as Ureaplasma urealyticum, Mycoplasma genitalium, HSV and trichomonas are being implicated in up 30 percent of cases. In a large portion of cases the etiology remains unknown. CDC guidelines recommend treating empirically for C. trachomatis, with azithromycin or doxycycline, in men with a positive urethral smear, however, cultures for C. trachomatis and gonorrhea should also be sent. If the Gram stain is uninformative, treatment for gonorrhea can be withheld pending culture results.
Bacterial Vaginosis (BV)
Debate continues over whether BV is truly a sexually transmitted disease, as it can be present in sexually inactive women. It is, however, a common cause of vaginitis in many sexually active women and is thus is discussed here briefly. The syndrome is caused by the replacement of normal vaginal flora with mixed flora (comprised of Gardnerella vaginalis, anaerobes, Mycoplasma hominis) resulting in symptoms in women. Diagnosis is made when three of four criteria are present: vaginal secretion pH > 4.5, fishy odor on KOH testing, "clue cells" on wet mount examination, and a homogeneous white discharge adherent to the vaginal wall. Women can be unaware of symptoms or complain of vaginal malodor and abnormal discharge. Male partners are not treated and there are only rare cases of men with symptoms from BV. Pregnant women should be treated for BV as infection has been associated with increased risk for preterm delivery and low birth rate infants.
STD Reporting in NYC
Reporting requirements vary by city and state. Reporting requirements for NYC are different than those for NY State. The NYC health code requires that both providers and laboratories report to the NYC Department of Health (DOH) the diagnosis of the eight reportable sexually transmitted diseases: gonorrhea, chlamydial infection, syphilis, PID, NGU, chancroid, LGV (Lymphogranuloma Venereum,) and LGI (Granuloma Inguinale). There are specific reporting forms that can be requested from the nursing supervisor in the AIM practice.