Sexually Transmitted Infections and Pelvic Inflammatory Disease
Philippe G. Judlin
Sexually transmitted infections (STIs) are still very frequent worldwide. Despite continuous progresses in treatment, screenings, prevention, and counseling, they are still on the rise in many developed countries and in the United States where about 1.6 million new cases occur each year.1 Effectively diagnosing and treating symptomatic and asymptomatic patients as well as their sexual partners can prevent complications associated with STIs and reduce the risk of disease transmission. However, therapeutic measures are insufficient because there is currently no cure for some of the most prevalent STIs (e.g., genital herpes and human papillomavirus [HPV] infections). Preventive measures such as screenings, patient counseling, and pre-exposure vaccinations have demonstrated benefits in the management of STIs. This chapter details the diagnosis, treatment, and prevention of the major STIs and pelvic inflammatory disease (PID).
SCREENINGS AND PREVENTIVE MEASURES
The U.S. Preventive Services Task Force (USPSTF) recommends that sexually active women younger than 25 years of age (including adolescents) have systematic annual screening for chlamydia, HIV, and gonorrhea (USPSTF recommendations for STI screening available at http://www.ahrq.gov/clinic/uspstf08/methods/stinfections.htm). Routine screening for herpes is not recommended because of potential high false-positive rates in low-risk populations.2
Chlamydia and gonorrhea infection rates are highest among females aged 15 to 19 years because adolescents, particularly those younger than the age of 15 years, are at high risk of acquiring STIs. Although biological factors such as cervical ectopy and lower levels of secretory immunoglobulin A (IgA), a local protective antibody in cervical mucus, have been postulated to contribute to this susceptibility, the evidence is not conclusive.3,4 Recurrent acquisition of STIs is common among adolescents, with many being reinfected within a few months of the index infection. It is estimated that 40% of the reported incidences of chlamydia and gonorrhea occur in adolescents previously infected with the organisms.5
In one study of sexually active adolescent women ages 14 to 17 years, 25% of the adolescents acquired their first STI (most commonly chlamydia) by the age of 15 years, and the median time interval between the first occurrence of intercourse and the first diagnosed STI was 2 years.6 STI screening for urban adolescent girls is recommended within the first year of sexual intercourse. Most adolescents in the United States can consent to the confidential diagnosis and treatment of STIs without parental consent or knowledge. There are a few states that require parental notification.
Many screening interventions have demonstrated a decline in chlamydial infections and the incidence of PID.7 Interval screening times for STIs vary. For patients with no history of an STI, the screening interval is based on changes in risk factor(s) or number of sexual partners. It is recommended that women with newly diagnosed chlamydial, gonococcal, or Trichomonas infections should be rescreened in 3 months to test for new asymptomatic infections. A patient’s sexual history should be included in the screening process to assess individual risk factors for STIs (see Table 6.11 for the required components of a sexual history for STI screening).
Although the burden of STIs is found primarily in younger populations, STI screenings are also recommended for older women who engage in high-risk sexual behavior. Postmenopausal women may not perceive themselves to be at risk for STIs although there is evidence that STI rates are increasing among older adults. Recent studies have found that the number of STIs among people older than age 45 years in the United Kingdom nearly doubled from 1996 to 2003.8 From 2004 to 2009 in the United States, the rates of chlamydia infections in women aged 45 to 54 years increased from 23 to 39.3 per 100,000 individuals, whereas syphilis increased from 4.6 to 8.5.1,9
Patient education and counseling are important tools for preventing STIs. Client-centered counseling in which a patient’s personal risk factors, situations in which the risk(s) occur, and having the patient or client set personal goals are effective in STI prevention. Training in client-centered counseling is available through the Centers for Disease Control and Prevention (CDC)
STD/HIV Prevention Training Centers (http://www.stdhivpreventiontraining.org). Abstinence and a reduction in the number of sexual partners are also reliable methods to avoid STIs. Counseling that encourages abstinence from sexual intercourse during the course of therapy for an STI is recommended.
STD/HIV Prevention Training Centers (http://www.stdhivpreventiontraining.org). Abstinence and a reduction in the number of sexual partners are also reliable methods to avoid STIs. Counseling that encourages abstinence from sexual intercourse during the course of therapy for an STI is recommended.
Consistent use of male condoms reduces the risk for some STIs, including chlamydia, gonorrhea, trichomoniasis, HSV-2, and HPV-associated diseases.10 In one prospective study among newly sexually active women in college, consistent and correct condom use was associated with a 70% reduction in risk for HPV transmission.11 Although data are limited, the female condom also reduces the risk of STIs.12
Although proper condom use is effective at preventing STIs, they are not 100% effective at preventing transmission. The rate of condom breakage has been reported to be 0.5 to 3.7% in several prospective studies, and inexperienced users may contribute to condom failure.13,14 There are two general categories of nonlatex condoms available in the United States. The first type is made of polyurethane or other synthetic material, can be substituted for latex condoms by those with latex allergies, and provides protection against sexually transmitted diseases (STDs)/HIV and pregnancy equal to that of latex condoms.15 Compared to latex condoms, pregnancy rates among women whose partners use polyurethane or other synthetic condoms are similar, but the polyurethane or other synthetic condoms are more expensive and are reported to have higher slippage and breakage rates than latex condoms.16
The second category of latex condom alternatives is natural membrane condoms (often referred to as natural or “lambskin” condoms). Lamb cecum is often the source for these condoms, and although the pores in these condoms do not allow sperm to pass through, they are more than 10 times the diameter of the HIV virus and 25 times the diameter of the HPV virus. Viral STIs can be transmitted despite use of these condoms, and they are not recommended for the prevention of STIs.15
Condoms lubricated with spermicides are no more effective than other lubricated condoms in protecting against the transmission of HIV and other STDs. Frequent use of nonoxynol-9 (N-9) may actually enhance susceptibility to HIV infection by causing a breakdown of the mucosal barrier.17 Therefore, use of condoms lubricated with N-9 is not recommended for STD/HIV prevention.
The cervical diaphragm demonstrated effectiveness in reducing cervical gonorrhea, chlamydia, and trichomoniasis transmission in observational studies.18 Diaphragms alone should not be relied upon for the prevention of HIV transmission. The vaginal contraceptive sponge offers some protection against cervical gonorrhea and chlamydia although use of the sponge has been associated with candidiasis. Vaginal spermicides containing N-9 are not effective in preventing cervical gonorrhea, chlamydia, or HIV.
Pre-exposure vaccination is one of the most effective methods for preventing transmission of several STIs. Hepatitis A virus (HAV), hepatitis B virus (HBV), and some types of HPV can all be effectively prevented with pre-exposure vaccination. Hepatitis A pre-exposure vaccination is recommended for men who have sex with men (MSM), intravenous drug users, and HIV-infected patients. Two vaccines against some types of HPV are available and are discussed more fully in Chapter 5, Abnormal Cervical Cytology and Human Papillomavirus. The 2006 Advisory Committee on Immunization Practices (ACIP) recommends universal hepatitis B immunization for all unvaccinated adults being evaluated for STIs. Vaccine trials for other STIs are being conducted.
Reporting and notification practices are instrumental in the management of STIs. All states require mandatory reporting of the major STIs to local and state health departments. Syphilis, gonorrhea, chlamydia, chancroid, acute hepatitis B and C, HIV, and AIDS are reportable diseases in every state. Reporting can be carried out by the provider and/or by the testing laboratory depending on state requirements. Clinicians should be aware of local reporting guidelines or should seek out local health departments or state STD programs for guidelines. Disease reporting can also assist in the management of sexual partners. When STI infection is suspected in a patient, all sexual partners should be notified, examined, and treated for the STD. According to the CDC, data are limited as to whether partner notification effectively decreases exposure to STDs or if it reduces the incidence and prevalence of these infections in a community.1 Treatment of partners, however, does decrease the risk of reinfection for the patient, so providers should at least encourage persons with STDs to notify their sex partners and urge them to seek medical evaluation and treatment.1 When a partner is unlikely to seek treatment for an STD, partnerdelivered patient medication (PDPM) can be used. In three clinical trials, the PDPM approach resulted in reduced prevalences of chlamydia (20%) and gonorrhea (50%) at follow-up.19, 20, 21 However, this approach has been criticized because the sexual partner does not receive counseling or screening for other STIs. Clinicians should be aware that PDPM is not legal in all states in the United States.
SEXUALLY TRANSMITTED INFECTIONS
Diseases Characterized by Genital Ulcers
In the United States, genital herpes is reported to be the most common ulcerative STI followed by syphilis. Other STIs characterized by genital ulcers include chancroid, lymphogranuloma venereum, and granuloma inguinale. Occasionally, primary infection with HIV or cytomegalovirus (CMV) can be associated with genital ulceration. More than one etiologic agent may be present
in genital, anal, or perianal ulcers, for example, herpes and syphilis. Painful ulcers are typically seen in genital herpes and chancroid, whereas painless ulcers are typically seen in syphilis, lymphogranuloma venereum, and granuloma inguinale; however, a clinical diagnosis cannot be made on this distinction. Approximately 25% of all patients presenting with genital ulcers will never have a specific etiologic agent identified. The CDC recommends that all patients with genital, anal, or perianal ulcers be evaluated with a serologic test for syphilis and a diagnostic evaluation for genital herpes; in settings where chancroid is prevalent, testing for Haemophilus ducreyi should also be performed. Evaluation for chancroid, granuloma inguinale, or LGV will be determined by the prevalence of these infections in the area where the STI was acquired, the risk profiles of the patient’s sexual contacts, and the patient’s travel history as well as those of their contacts. HIV testing should be performed on all persons with genital, anal, or perianal ulcers who are not known to have HIV infection. Further screening for Chlamydia trachomatis, Neisseria gonorrhoeae, HIV, and Hepatitis B and C is also recommended for patients with genital ulcers.
in genital, anal, or perianal ulcers, for example, herpes and syphilis. Painful ulcers are typically seen in genital herpes and chancroid, whereas painless ulcers are typically seen in syphilis, lymphogranuloma venereum, and granuloma inguinale; however, a clinical diagnosis cannot be made on this distinction. Approximately 25% of all patients presenting with genital ulcers will never have a specific etiologic agent identified. The CDC recommends that all patients with genital, anal, or perianal ulcers be evaluated with a serologic test for syphilis and a diagnostic evaluation for genital herpes; in settings where chancroid is prevalent, testing for Haemophilus ducreyi should also be performed. Evaluation for chancroid, granuloma inguinale, or LGV will be determined by the prevalence of these infections in the area where the STI was acquired, the risk profiles of the patient’s sexual contacts, and the patient’s travel history as well as those of their contacts. HIV testing should be performed on all persons with genital, anal, or perianal ulcers who are not known to have HIV infection. Further screening for Chlamydia trachomatis, Neisseria gonorrhoeae, HIV, and Hepatitis B and C is also recommended for patients with genital ulcers.
A diagnosis of any STI based only on the patient’s medical history and physical examination is frequently inaccurate. Despite this, clinicians often empirically treat for the diagnosis considered most likely based on clinical presentation and history (including travel history) while awaiting laboratory results.
Herpes Simplex
Herpes simplex virus (HSV) infection is one of the most prevalent STIs with rare but serious medical consequences such as neonatal infection and an increased risk (two- to four-fold) of acquiring HIV infection when herpes simplex virus type II (HSV-2) is present.22 Genital herpes is also associated with significant psychological and psychosexual morbidity and is a chronic, lifelong disease.23 Around 50 million adults in the United States report a history of genital herpes infection.24 Genital infection can be caused by either herpes simplex virus type I (HSV-1), associated with oral/facial lesions, or HSV-2. Both HSV-1 and HSV-2 can be transmitted to other mucosal sites or through abraded skin by direct contact with infected secretions or autoinoculation. Although the average incubation period after exposure is 4 days, the incubation period of HSV-1 and HSV-2 ranges from 2 to 12 days.25
The majority of HSV-2 infections are asymptomatic or undiagnosed because the infections are subclinical. However, intermittent viral shedding in the genital tract does occur and represents an opportunity for transmission. Because of this, the majority of genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs. The frequency of viral shedding is influenced by the serotype present, the type of infection (primary or nonprimary), and time elapsed since the primary clinical infection. HSV-2 infections are associated with more frequent and prolonged periods of shedding than HSV-1 infections.26
HSV-1 is typically transmitted during childhood via nonsexual contact. As with HSV-2, most HSV-1 infections are subclinical. Acquisition of genital HSV-1 appears to be increasing, however, because recent studies have shown that up to 30 to 40% of new genital infections among women may be caused by HSV-1, particularly in adolescent and young adults.24,27 Studies show that genital herpes caused by HSV-1 is increasing in the United States as well as in other developed countries.28,29
Clinical Symptoms
HSV infections may be classified into four groups: primary initial infection, nonprimary initial infection, recurrent infection, and subclinical infection (asymptomatic shedding). A primary infection occurs when a person without antibodies to HSV-1 and HSV-2, that is, they were seronegative, becomes infected. Although the primary outbreak of herpes can be asymptomatic, clinical signs may appear within 2 to 14 days of contact. The clinical manifestations of primary genital HSV infection are highly variable and tend to be more apparent in women than men. Mucoepithelial lesions are present and may be multiple and bilateral, starting as papules, progressing to vesicles, and erupting in painful ulcers. In 2 to 20% of patients, extragenital lesions, for example, aseptic meningitis, urinary retention, and distant skin lesions are also present. Fever, headache, malaise, myalgia, dysuria, and even tender lymphadenopathy are often present. It takes an average of 19 days for complete resolution of the ulcerative lesions to occur.
Because primary herpes infection is often associated with a prolonged clinical illness with severe genital ulcerations, all patients with a suspected primary episode of HSV should be treated with antiviral therapy. Therapy begun within 72 hours of the appearance of lesions may decrease the duration and severity of the illness by days or weeks as well as the risk of complications.30 Up to 25% of patients presenting with a first clinical episode of herpes infection have serologic evidence of a past HSV-2 infection, which was asymptomatic.31
Nonprimary initial infection refers to the acquisition of HSV-1 in a patient who has previously been infected with HSV-2 or acquisition of HSV-2 in a patient who has previously been infected with HSV-1. The symptoms of nonprimary initial infections may be less severe than primary infection and systemic symptoms, most likely because antibodies against one type of HSV infection afford some protection against the other.
After primary infection with HSV, the virus becomes latent in sensory nerve ganglion. Recurrent infections are the result of symptomatic and asymptomatic viral shedding when reactivated virus travels the sensory nerve
from a nerve ganglion to the mucoepithelial surface. Recurrent infections are less severe, more likely to be unilateral, lack systemic symptoms, and are of shorter duration than primary or nonprimary infections. In the first year after the latency period, untreated HSV-2 infection has a median recurrence rate of four episodes, whereas HSV-1 is associated with a median recurrence rate of one episode.23 The frequency of recurrence depends on the severity and duration of the initial episode, the infecting serotype, and the host immune response. Trigger factors for recurrent outbreaks vary from person to person and can include fever, menses, emotional stress, or local trauma. Although systemic symptoms are uncommon, prodromal symptoms, including vulvar burning, tingling, itching, and hypersensitivity, may be present prior to the appearance of lesions. The length of viral shedding is shortened in recurrent infections, usually lasting 5 to 10 days without antiviral therapy. Antiviral therapy that is started within 24 hours of the first prodromal sign or symptom increases the likelihood that the recurrence will resolve without the development of lesions.
from a nerve ganglion to the mucoepithelial surface. Recurrent infections are less severe, more likely to be unilateral, lack systemic symptoms, and are of shorter duration than primary or nonprimary infections. In the first year after the latency period, untreated HSV-2 infection has a median recurrence rate of four episodes, whereas HSV-1 is associated with a median recurrence rate of one episode.23 The frequency of recurrence depends on the severity and duration of the initial episode, the infecting serotype, and the host immune response. Trigger factors for recurrent outbreaks vary from person to person and can include fever, menses, emotional stress, or local trauma. Although systemic symptoms are uncommon, prodromal symptoms, including vulvar burning, tingling, itching, and hypersensitivity, may be present prior to the appearance of lesions. The length of viral shedding is shortened in recurrent infections, usually lasting 5 to 10 days without antiviral therapy. Antiviral therapy that is started within 24 hours of the first prodromal sign or symptom increases the likelihood that the recurrence will resolve without the development of lesions.
Asymptomatic viral shedding is very frequent in HSV-infected patients and has been found in both men and women with no evidence of genital lesions.32,33 Viral shedding appears to be more frequent in people with symptomatic recurrences compared to those who are asymptomatic. In one study, persons with asymptomatic HSV-2 infection had a shedding rate of 10.2% compared with a rate of 20.1% among persons with symptomatic genital herpes.33 Subclinical HSV shedding is the major cause of sexual transmission of HSV because infected persons are unaware that they have the infection or they are asymptomatic when transmission occurs.
Diagnosis
Diagnostic testing for HSV includes viral culture, polymerase chain reaction (PCR) assays, direct fluorescent antibody (DFA), and Tzanck preparation. Clinical diagnosis has a maximum sensitivity of 39% and results in a false-positive diagnosis in about 20% of patients; therefore, confirmatory testing using viral or serologic tests is required.2,34 Cell culture and PCR are the preferred diagnostic tests for HSV. A swab taken from the base of a lesion (vesicles will need to be unroofed prior to obtaining the swab) may be tested for HSV using viral culture, HSV antigen testing, or PCR testing for HSV DNA. If a viral culture is taken, the specimen must be refrigerated and rapidly transported to the laboratory, and isolates usually grow within 5 days. Viral cultures have low sensitivity, especially for recurrent lesions or lesions that have already started to heal. Vesicles contain the highest viral concentrations in the first 24 to 48 hours after presentation. Although a positive culture is a definitive diagnosis, a negative culture does not rule out the diagnosis of HSV infection. PCR assays are more sensitive than viral culture, less dependent on transport situations, and are significantly faster than viral culture.35,36
For DFA testing, viral samples can be obtained from a vesicle by swabbing; however, scraping the base with a blade is preferable to increase the yield of infected cells. The specimen should be spread over the center of a glass slide that is then air dried, fixed, and sent to the laboratory for testing. Positive results using DFA testing may be obtained within 24 hours. The use of Tzanck preparation to detect cellular changes of HSV infection is neither specific nor sensitive (less than 50%) and should not be relied upon.
Type-specific and non-type-specific antibodies to HSV develop during the first several weeks to months of infection and persist indefinitely. Older assays that are still available for serologic testing for HSV may not accurately distinguish between HSV-1 and HSV-2. Health care providers using serologic testing for HSV infections should ask for serologic type-specific glycoprotein G (gG)-based assays to be done.37,38 Lab tests and point of care testing using gG-based type-specific tests for the detection of HSV-2 antibodies are available. The sensitivities of these serologic tests to detect HSV-2 antibody vary from 80 to 98% and false-negative tests may occur, especially during the early stages of infection.39 Immunoglobulin M (IgM) testing for HSV is not useful because it is not type-specific, and positive tests may occur during recurrent episodes of herpes.
Currently, routine screening for HSV-2 is not recommended because there may be a high false-positive rate in low-risk populations, and there are no formal guidelines on how to reconcile test results.2 Hence, routine testing would create a great deal of uncertainty and confusion.
However, the type-specific serologic tests may be used to confirm a clinical diagnosis of genital herpes, particularly if a false-negative HSV culture is suspected. In addition, these tests can be used to diagnose atypical lesions or in patients with recurrent genital symptoms.1 They are also used to detect unrecognized infection and to manage the sex partners of persons with genital herpes. The use of testing to determine HSV type has been suggested for pregnant women at risk of acquiring herpes in the third trimester, for monogamous couples seeking ways to minimize transmission, for the diagnosis of recurrent genital eruptions, and for identifying HSV as a risk factor for HIV transmission in high-risk patients.
Treatment
Antiviral chemotherapy for herpes simplex infection provides clinical benefits to most symptomatic patients. The CDC recommendations for antiviral treatment and prophylaxis are listed in Table 6.1. Empiric antiviral therapy is recommended for all cases of suspected primary HSV infection. Even in primary infection cases with mild clinical manifestations, antiviral therapy is recommended because these patients can develop severe or prolonged symptoms. The first clinical outbreak of
herpes may require hospitalization for pain control and possibly bladder catheterization to treat dysuria secondary to sacral nerve root involvement. Dysuria can be treated by intermittent or indwelling bladder catheterization over the course of several days. In addition to topical anesthetics (e.g., viscous lidocaine) applied to the lesions, the use of oral or intravenous painkillers including analgesics and narcotics may be necessary. Other symptomatic measures include applying warm compresses and sitz baths for patients with severe dysuria secondary to multiple ulcerations.
herpes may require hospitalization for pain control and possibly bladder catheterization to treat dysuria secondary to sacral nerve root involvement. Dysuria can be treated by intermittent or indwelling bladder catheterization over the course of several days. In addition to topical anesthetics (e.g., viscous lidocaine) applied to the lesions, the use of oral or intravenous painkillers including analgesics and narcotics may be necessary. Other symptomatic measures include applying warm compresses and sitz baths for patients with severe dysuria secondary to multiple ulcerations.
TABLE 6.1 Recommended Regimen for the Treatment of Genital Herpes Infections | |||||||||||||||||||||
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Intravenous antiviral medication is indicated in severe primary outbreaks or in disseminated herpetic infections. The following clinical criteria during primary HSV infection warrant initiation of parenteral therapy:
Central nervous system (CNS) disease such as aseptic meningitis, encephalitis, or transverse myelitis
End organ disease including hepatitis and pneumonitis
Disseminated HSV
To treat complicated HSV, the CDC recommends intravenous acyclovir (5 to 10 mg/kg) every 8 hours for 2 to 7 days or longer until evidence of clinical improvement, followed by oral antiviral therapy to complete at least 10 days of therapy.1 In instances of impaired renal function, the dose of acyclovir will need to be adjusted. Oral treatment can be extended for more than 10 days if lesions are not completely healed. Topical therapy with antiviral drugs offers no/poor clinical benefit and should not be used.
Systemic antiviral drugs partially control the signs and symptoms of herpes episodes when used to treat recurrent clinical outbreaks or when prescribed as daily suppressive therapy. However, these drugs neither eradicate the virus nor affect the pattern of recurrences and risk of transmission once they are discontinued. Clinical trials have shown that acyclovir, valacyclovir (the valine ester of acyclovir with enhanced absorption after oral administration) and famciclovir provide equal clinical benefit in the treatment of genital herpes. Famciclovir may be less effective in suppression of viral shedding however.40 Famciclovir and valacyclovir allow for less frequent dosing compared to acyclovir; however, acyclovir is less expensive. When oral antiviral therapy is initiated within 24 hours, the recurrence of lesions may be aborted or at least the duration and severity of symptoms decreases significantly. The initial suggested treatment duration for recurrent herpes was 5 days, but studies have shown that shorter treatment times with famciclovir (1000 mg twice a day for 1 day), acyclovir (800 mg three times a day for 2 days), or valacyclovir (500 mg twice a day for 3 days) are effective alternatives.41, 42, 43 Topical therapy with antiviral drugs offers no clinical benefit and should not be used. Allergic reactions or other adverse effects with famciclovir, valacyclovir, and acyclovir are rare. A desensitization regimen for acyclovir has been described.44
After a primary infection or in instances of recurrent infection, antiviral therapy may be given as suppressive therapy to reduce the frequency of recurrences or episodically to ameliorate or shorten the duration of lesions. Patients may choose to take episodic therapy at the first signs of a recurrent outbreak (prodromal symptoms) or they may opt for continuous suppressive therapy in case of frequent recurrences (i.e., at least six recurrences per year). Episodic therapy with acyclovir, famciclovir, or valacyclovir has shown to decrease the proportion of patients with outbreaks, reduce the duration of symptoms, and shorten the duration of viral shedding. Patients who self-initiate therapy receive a greater clinical benefit with episodic therapy than patients who initiate treatment within 48 hours of lesion appearance.
Suppressive therapy reduces the frequency of genital herpes recurrences by 70 to 80% among patients who have frequent recurrences (more than six clinical episodes per year), and many patients report no symptomatic outbreaks.45 Daily antiviral therapy reduces viral shedding and the risk of transmission to an uninfected sexual partner. Patients taking suppressive therapy rate their quality of life higher compared to those on episodic therapy.46,47 Valacyclovir, famciclovir, and acyclovir appear to have similar benefits in providing suppressive therapy.
Compared to episodic therapy, suppressive therapy has the additional advantage of decreasing the risk for genital HSV-2 transmission to susceptible partners.48 In couples where there is discordance for HSV-2 infection,
suppressive therapy should be considered as part of an overall strategy for reducing transmission; consistent condom use and avoidance of sexual activity during outbreaks should also be observed.
suppressive therapy should be considered as part of an overall strategy for reducing transmission; consistent condom use and avoidance of sexual activity during outbreaks should also be observed.
Treatment regimens can be determined by the frequency of episodes, severity of symptoms, and whether the patient has an uninfected partner. Ease of administration and cost are important considerations for prolonged treatment.
Counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management. The goals of counseling are to help patients both cope and manage their infection(s) and prevent sexual and perinatal transmission. Counseling should include information about the natural course of the disease, the possibility of recurrences, the significance of asymptomatic viral shedding, and the availability of suppressive or episodic therapy. All patients with herpes should be counseled to inform their current (and any future) sex partners and to abstain from sexual activity with uninfected persons when prodromal symptoms or lesions are present. Patients should be informed that consistent and correct use of latex condoms may decrease transmission. Sexual partners should be informed that they may be infected even if they have no symptoms. (In instances where it is not known if the sexual partner is infected, type-specific serologic testing of the asymptomatic partners of persons with genital herpes can help determine whether such partners are already HSV seropositive or whether risk for acquiring HSV exists.) The risks of neonatal HSV infection should be explained to everyone diagnosed with HSV, including men. All patients with HSV-2 seropositivity are at increased risk for HIV acquisition and should be told this. They should also be informed that suppressive antiviral therapy does not reduce the increased risk for HIV acquisition associated with HSV-2 infection.49,50
Special Considerations
Pregnancy
Because of the potential for neonatal morbidity and mortality with vertically acquired infection, all pregnant women should be asked if they have a history of herpes or if their partners do. Approximately 1 to 2% of susceptible women acquire HSV during pregnancy and most new infections are asymptomatic.51 Among women with a history of recurrent outbreaks, 75% will have at least one recurrence during pregnancy and approximately 14% will have prodromal symptoms or clinical recurrence at the time of delivery.52
The CDC recommends that pregnant women who are not known to be infected with HSV-2 should abstain from intercourse with men who have genital herpes during the third trimester of pregnancy.1 Similarly, pregnant women who are not known to have orolabial herpes should avoid receptive oral sex from partners known to have orolabial herpes infections and genital exposure to HSV-1 during the third trimester.
Approximately 80% of infected neonates are born to mothers with no known history of genital herpes. The risk of transmission to the neonate from an infected mother is high (30 to 50%) among women who acquire genital herpes near the time of delivery and low (less than 1%) among women with histories of recurrent herpes at term or who acquire genital HSV during the first half of pregnancy.51,53 For women with recurrent lesions at the time of delivery, the rate of neonatal transmission with vaginal delivery is 3%.54 However, because recurrent genital herpes is much more common than primary herpes infection, the proportion of neonatal herpes infections acquired from a mother with recurrent herpes is substantial, and the majority of mothers lack histories indicating clinical evidence of genital herpes.
A primary outbreak in the first trimester of pregnancy has been associated with chorioretinitis, microcephaly, and in rare cases, skin lesions. Oral antiviral therapy may be administered to pregnant women with mild or moderate primary outbreaks to reduce the duration and severity of symptoms as well as to decrease viral shedding. For more severe primary outbreaks, oral therapy may be extended for more than 10 days if the lesions are not healed at that time. In severe or disseminated maternal infections, intravenous therapy may be administered.
The use of suppressive therapy late in pregnancy reduces the frequency of recurrent infection by 75%, and the rate of cesarean delivery for recurrent herpes is reduced by 40%.55 Women with active recurrent herpes should be offered suppressive viral therapy (acyclovir 400 mg orally three times a day or valacyclovir 500 mg twice a day) at or beyond 36 weeks and continue until delivery. It should be noted that these doses are higher than those used in nonpregnant women for suppression. No data support the use of antiviral therapy among HSV seropositive women without a history of genital herpes.
Syphilis
Syphilis is a reportable STI in the United States. The majority of syphilis infections are seen in MSM, although increases occurred in heterosexual populations from 2001 to 2009.1 The South accounts for about 46% of the national cases of primary and secondary (P&S) syphilis in 2010.
Syphilis is caused by the spirochete Treponema pallidum and is primarily acquired through contact with an infectious lesion. Only a few T. pallidum organisms are required to infect abraded skin. The lesions of P&S syphilis include chancres, mucous patches, and/or condylomata lata, all of which are highly infectious. The risk of infection to a partner of an infected person is approximately 30 to 33%.56 Syphilis may also be spread by kissing or via contact with lesions on the lips, on or
in the oral cavity, or on the genitals. T. pallidum is very labile and syphilis cannot be spread through contact with inanimate objects such as toilet seats or sex toys.
in the oral cavity, or on the genitals. T. pallidum is very labile and syphilis cannot be spread through contact with inanimate objects such as toilet seats or sex toys.
Based on clinical findings, the infection is divided into (overlapping) stages: primary, secondary, latent, and tertiary. In primary infection, the lesions present as an ulcer or chancre at the primary infection site. Neurologic infection may present at any time after initial infection and may present clinically as cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities. In secondary infection, the manifestations may include skin rash, lymphadenopathy, or mucocutaneous lesions, to name a few. Tertiary infections present as cardiac or gummatous lesions.
Latent infections are those that are diagnosed by serologic testing alone and are classified as either early latent (infection acquired within the preceding year), late latent (infection acquired over a year ago), or latent syphilis of unknown duration. Patients with early latent infection are considered to be potentially infectious, whereas those with late latent infection are not likely to transmit the disease. Misclassification of latent syphilis is common. Although there have been proposals to distinguish early latent infection from late latent infection on the basis of nontreponemal titers, this is not a reliable distinguishing feature.1
All patients who have syphilis should be tested for HIV. In areas where the prevalence of HIV is high, patients with primary syphilis should be retested for HIV after 3 months if their initial HIV test was negative.
Clinical Symptoms
Syphilis has been called “the great imitator.” It can present in patients at any stage with nonspecific symptoms. The trademark of primary syphilis is the chancre—a solitary, indurated, and painless ulceration that occurs at the site of inoculation of the spirochete after an incubation period of 10 to 90 days. The chancre is a 1- to 2-cm ulcer that is indurated with a smooth base and raised, firm borders. There is no exudate unless secondary infection occurs. There is little pain or bleeding if the lesion is scraped. The chancre may occur in the cervix, vagina, vulva, anus, or on nongenital sites such as the oropharynx. When the chancre is located on the cervix or in the vagina, it can go unnoticed by the patient. Thus, women may be unaware of the infection until serologic testing is performed. Multiple chancres can occur particularly in patients infected with HIV. The tissue destruction that occurs in syphilis is caused by the immune response to T. pallidum. If untreated, the primary chancre resolves spontaneously within 3 to 6 weeks. Although the mechanism of healing is unknown, local immune responses are believed to be responsible. The chancre represents the local, initial infection with syphilis, but during this primary stage of syphilis, widespread dissemination of the infection may occur.
In the absence of therapy, approximately 25% of patients will develop the secondary stage of syphilis 6 weeks to 6 months later. During secondary syphilis, the spirochetes multiply and spread throughout the body. Secondary syphilis is associated with a wide variety of symptoms but is often characterized by low-grade fever, malaise, lymphadenopathy, and rash. The primary chancre may still be present, particularly in HIV-infected patients.
Lymphadenopathy may be found in the posterior cervical, axillary, inguinal, and femoral regions. Nodes are tender, firm, and have a rubbery consistency. Epitrochlear adenopathy, a rare occurrence, should strongly raise suspicions for the diagnosis of syphilis.
The nature of the rash in secondary syphilis is variable. It may be macular, maculopapular, papular, or pustular. Nodular lesions may also be seen. With the exception of congenital syphilis, it is never vesicular. It may occur anywhere on the body including the palms of the hands and soles of the feet. Lesions may be present in areas closest to the primary chancre and are often scaly, red or reddishbrown, and measure 0.5 to 2 cm in diameter. In warm, moist areas of the body such as mucous membranes in the mouth and perineum, gray to white plaques called “condylomata lata” may develop. They are highly infectious as are mucous patches that may develop as silvery gray, shallow ulcerations with a raised red border. Patchy alopecia may be present on the scalp, eyebrows, or beard.
Severe complications from syphilis include syphilitic hepatitis, infiltrated or ulcerated gastrointestinal tract, anterior uveitis or panuveitis, synovitis, osteitis, periostitis, and renal involvement in the form of immunecomplex glomerulonephritis or nephritic syndrome. During the secondary stage, there is hematogenous and lymphatic dissemination of the spirochete. If left untreated, the symptoms of secondary syphilis will resolve spontaneously.
An asymptomatic latent phase follows secondary syphilis and is variable in duration. The CDC defines early latent phase as latent infection acquired within 1 year, whereas the World Health Organization (WHO) defines early latent phase as infection of less than 2 years. Syphilis is sexually communicable by patients in primary, secondary, or early latent stages. The late latent stage is unlikely to be sexually contagious but can be transmitted to a fetus transplacentally. Latent syphilis is often misclassified. It has been proposed that latent syphilis be characterized as “high-titer” or “lowtiter” syphilis; however, early latent syphilis and late latent syphilis cannot be distinguished based solely on titers in nontreponemal tests.1
If syphilis is untreated, approximately 25 to 40% of infected patients will develop tertiary syphilis. Clinical manifestations of tertiary syphilis may occur as early as 1 year or as late as 25 years after primary infection. Tertiary syphilis is characterized by the involvement and progressive destruction of the cardiovascular
system (often the ascending thoracic aorta), CNS, and/or the musculoskeletal system. Various organ systems may develop gummata (late benign tertiary syphilis). Cardiovascular syphilis typically occurs 10 to 30 years after initial infection and results in a dilated aorta and aortic valve regurgitation. A high-pitched “tambour” second sound may be detected upon physical examination and chest films often show a calcified ascending arch of the aorta not typical of arteriosclerotic disease. Syphilis may also involve the coronary arteries.
system (often the ascending thoracic aorta), CNS, and/or the musculoskeletal system. Various organ systems may develop gummata (late benign tertiary syphilis). Cardiovascular syphilis typically occurs 10 to 30 years after initial infection and results in a dilated aorta and aortic valve regurgitation. A high-pitched “tambour” second sound may be detected upon physical examination and chest films often show a calcified ascending arch of the aorta not typical of arteriosclerotic disease. Syphilis may also involve the coronary arteries.
Neurosyphilis can occur during tertiary syphilis but may occur at any time during the course of the disease. Involvement of the CNS in early stages of syphilis may present as asymptomatic meningitis, symptomatic meningitis, and meningovascular disease; it is frequently seen in patients with concurrent HIV infection. Early neurosyphilis may also present as symptomatic meningitis, ocular neurosyphilis (most commonly, posterior uveitis), hearing loss (with or without tinnitus), and meningovascular syphilis which may present as an ischemic stroke in a young individual.
Currently, CNS involvement is the most common manifestation of tertiary syphilis, but it is also the most difficult to diagnose and to treat. Neurosyphilis is often divided into meningeal, vascular, and parenchymatous forms (the latter including tabes dorsalis and general paresis). The meningeal and vascular may occur together (meningovascular syphilis), is an inflammatory process, and is seen more frequently compared to the parenchymal forms. Meningovascular syphilis usually occurs within 10 years of infection (often between years 4 and 7) and may cause strokes. Unlike other causes of strokes, meningovascular syphilis may cause prodromal symptoms that may be present for months before the actual cerebral infarction. Stroke symptoms can be either acute or subacute in onset.57
Tabes dorsalis, or locomotor ataxia, occurs with syphilitic involvement of the posterior columns of the spinal cord and of the dorsal roots. The most frequent symptoms of tabes dorsalis are sensory ataxia and sudden onsets of severe, stabbing pain in the limbs, back, or face. The general paresis is a progressive, dementing illness. On physical examination, dysarthria; facial and limb hypotonia; intention tremors of the face, tongue, and hands; and reflex abnormalities may be seen. Pupillary abnormalities, for example, the Argyll Robertson pupil (the pupil does not react to light but accommodates, dilates imperfectly to mydriatics, and does not dilate in response to painful stimuli) may also be present. Many patients with neurosyphilis are asymptomatic.
Recommendations for lumbar puncture testing to ascertain CNS involvement in syphilis are in Table 6.2. The cerebrospinal fluid (CSF) abnormalities occurring in neurosyphilis include pleocytosis (45 white blood cell [WBC] per high-power field), low glucose (2/3 serum glucose), and elevated protein (445 mg/dL). In up to 4% of patients with symptomatic neurosyphilis, these tests may be normal.58 False-positive Venereal Disease Research Laboratory (VDRL) testing of the CSF is rare but may occur if there is contamination of the specimen with blood. False-negative VDRL testing may occur in up to 70% of patients with neurosyphilis. Testing using CSF fluorescent treponemal antibody absorption (FTA-ABS) analysis is controversial, and its use has been discouraged because it may lead to the overdiagnosis of neurosyphilis. However, a reactive serum FTA-ABS with a nonreactive CSF FTA-ABS makes neurosyphilis unlikely. The CSF FTA-ABS, particularly when combined with an elevated CSF B-cell count (elevation in CSF CD191 cells), is most useful in whom neurosyphilis is suspected, but the CSF VDRL is nonreactive.59
TABLE 6.2 Recommendations for Lumbar Puncture With Cerebrospinal Fluid Examination in Syphilis | ||||
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If CSF pleocytosis was present on the initial evaluation, a CSF examination should be done every 6 months to ascertain treatment success.1 Changes in the CSF protein or CSF VDRL occur more slowly than normalization of cell counts. Failure of the CSF cell count to decrease in the first 6 months or lack of resolution of CSF pleocytosis after 2 years should prompt retreatment. When treatment failure is indicated in cardiovascular and gummatous syphilis, another course of benzathine penicillin is required, whereas neurosyphilis usually requires 14 days of intravenous penicillin G.1
Tertiary syphilis expresses gummas, which are lesions with a coagulated, necrotic center resulting in small-vessel obliterative endarteritis. Gummas may present anywhere, including the skin, bones, and visceral organs. Visceral gummas may present as a mass lesion. Gummatous syphilis is the most uncommon type of late syphilis.
Diagnosis
T. pallidum cannot be cultured in a laboratory so diagnosis must be made by direct visualization of the organism via darkfield examination, serology, or DFA testing. Darkfield examination and direct fluorescent antibody test for Treponema pallidum (DFA-TP) of lesion exudate or tissue sample are definitive methods for early diagnosis of syphilis. Darkfield examination is
recommended for patients with a chancre because serologic testing may be nonreactive during initial infection. Darkfield examination has a specificity of 70 to 95%, depending on the expertise of the operator; a positive examination requires the presence of at least 10 organisms in the specimen.60 DFA-TP is specific for T. pallidum antigens but requires a fluorescence microscope and a trained and experienced technologist. In both of these methods, it is important to note that a negative test does not totally exclude the diagnosis of syphilis.
recommended for patients with a chancre because serologic testing may be nonreactive during initial infection. Darkfield examination has a specificity of 70 to 95%, depending on the expertise of the operator; a positive examination requires the presence of at least 10 organisms in the specimen.60 DFA-TP is specific for T. pallidum antigens but requires a fluorescence microscope and a trained and experienced technologist. In both of these methods, it is important to note that a negative test does not totally exclude the diagnosis of syphilis.
The diagnosis of syphilis is most commonly made using serologic-based testing. Because serologic testing depends on a humoral immune response to infection, it is an indirect method of testing. Serologic testing involves a two-step process, beginning with a nonspecific test and concluding with a treponeme-specific test (Table 6.3). Nontreponemal tests assess reactivity of patient serum to a cardiolipin-cholesterol-lecithin antigen. The nontreponemal screening tests include the VDRL, rapid plasma reagin (RPR), automated reagin test (ART), and toluidine red unheated serum test (TRUST). The sensitivities of all serologic tests are less than 90% in primary syphilis when antibody responses may still be developing.61 The sensitivity of these tests increases with the duration of infection.
When using serologic assays to diagnose syphilis, it should be noted that IgM and immunoglobulin G (IgG) antitreponemal antibodies may respectively take 2 and 4 weeks to appear postinfection. Nontreponemal tests are semiquantitative, and antibody titers, which usually correlate with disease activity, should be reported quantitatively. A four-fold change in titer, equivalent to a change of two dilutions (e.g., from 1:16 to 1:4 or from 1:8 to 1:32), is considered necessary to demonstrate a clinically significant difference between two nontreponemal test results that were obtained using the same serologic test. Sequential serologic tests in individual patients should be performed using the same testing method, and, if possible, in the same laboratory. The VDRL and RPR are equally valid assays, but quantitative results from the two tests cannot be compared directly because RPR titers frequently are slightly higher than VDRL titers. Treatment accelerates the pace of antibody decline although titers will naturally decline without treatment. In some people, nontreponemal antibodies can persist for a long period of time—a response referred to as the “serofast reaction.”
TABLE 6.3 Interpretation of Serologic Testing for Syphilis | |||||||
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Nonspecific tests (VDRL, RPR, ART, or TRUST) may be falsely negative early in the course of the infection before serum antibodies have developed or when a prozone phenomenon occurs. A prozone reaction occurs when high antibody titers interfere with the formation of antigen-antibody complexes during agglutination, resulting in an overabundance of nonbinding antibodies and a negative reaction. A negative nontreponemal test can occur in up to 40% of infected patients.60 Testing should be repeated 1 to 2 weeks after a negative test result if clinical suspicion is high.
False-positive results using nontreponemal testing may occur with other disease states or physiologic conditions. Any strong immunologic stimuli, including recent vaccinations, acute viral or bacterial infections, intravenous drug use, tuberculosis, chronic liver disease (CLD), autoimmune disorders, and connective tissue diseases, may cause a false-positive reaction. False-positive tests are particularly common during pregnancy. Diseases due to other treponemes (e.g., Lyme disease) may also cause false-positive treponemal test results. Tests may be falsely positive up to 6 months due to these conditions. Approximately 1 to 2% of patients in the United States will have a false-positive nontreponemal test. Because the current incidence of syphilis is low, the majority of positive screening tests will not be due to treponemal infection.
Treponemal-specific tests are necessary to confirm the diagnosis of syphilis after a positive nontreponemal test result in order to avoid treating false positives. Treponemal-specific tests include FTA-ABS, microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP), Treponema pallidum particle agglutination assay (TP-PA), and Treponema pallidum enzyme immunoassay (TP-EIA). These qualitative tests are specific for T. pallidum antigens and are reported as reactive or nonreactive. The TP-PA is more commonly used than the FTA-ABS because it is less expensive and simpler to perform. Treponemal tests are only applicable to patients with no previous history of syphilis and should not be used to assess treatment response. In the majority of patients (75 to 80%), once a specific treponemal test is positive, it stays positive for life. When both the nontreponemal and treponemal tests are reactive, a
diagnosis of syphilis is confirmed unless prior treatment history rules out a diagnosis.
diagnosis of syphilis is confirmed unless prior treatment history rules out a diagnosis.
Newly acquired syphilis infection can be diagnosed in patients who were previously treated if RPR testing reveals a four-fold increase in titer. The CDC recommends that all titers be compared using the same test methodology in the same laboratory to avoid variation of test results. Reinfection can be diagnosed using the following criteria:
Prior history of an appropriate treatment regimen
Clinical manifestations of either primary or secondary syphilis
History of new risk factors
A four-fold decline in RPR titers after retreatment (If possible, all titers should be compared using the same test methodology.)
For discordant test results, the CDC has several recommendations to guide patient management.1 For patients with no history of treatment who have a positive treponemal test and a negative nontreponemal test, a second differential treponemal test should be done. If the second treponemal test is negative, the clinician decides, based on history, if further evaluation or treatment is necessary or, alternatively, they may choose to perform a third treponemal test. If the second treponemal test is positive, clinicians should offer treatment for late latent infection and, unless history or physical examination suggests otherwise, the patients may be considered unlikely to be infectious. For patients with a history of treatment for syphilis, a negative nontreponemal test will require no further management or testing unless their sexual history suggests a risk of reexposure.
Rapid care testing for T. pallidum infection has not been approved by the U.S. Food and Drug Administration (FDA) for routine syphilis testing. A performance comparison of nine different rapid tests demonstrated that test sensitivity ranges from 85 to 98% and specificity ranges from 93 to 98%.62 Although these tests are low cost and highly sensitive and specific, they cannot distinguish between active and treated syphilis.
TABLE 6.4 Treatment of Syphilis | |||||||||||||||||||||||||
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Treatment
T. pallidum has a slow metabolism and divides slowly, averaging one doubling in vivo per day. Long-lasting penicillin G in benzathine, aqueous procaine, or aqueous crystalline form is the drug of choice for treatment of all stages of syphilis (see Table 6.4 for treatment protocols for syphilis). Because of the high rate of failure of other treatment modalities, particularly in pregnancy, it is recommended that patients with known penicillin allergy undergo desensitization with subsequent administration of penicillin.1 An oral desensitization protocol is available in Table 6.5. Clinicians should inform patients that if antibiotic therapy is stopped for more than 24 hours, repeat desensitization is required if penicillin is to be used again. The first dose of benzathine penicillin should be given via the intramuscular route at the completion of the oral desensitization protocol.
Only the long-acting forms of benzathine penicillin should be used for syphilis treatment because it provides continuous low doses of penicillin. It is administered intramuscularly (IM) because intravenous administration has been associated with cardiopulmonary arrest and death. Bicillin L-A (2.4 million units of benzathine penicillin G) has demonstrated detectable serum concentrations for up to 30 days. In contrast, Bicillin C-R (equal concentrations of procaine and benzathine penicillin G) should not be used to treat syphilis because serum drug levels last for only 7 days. If patients treated for late or latent syphilis miss a dose, an interval of 10 to 14 days may be acceptable before the treatment regimen should be restarted.1
Within hours after antibiotic treatment, patients can develop an acute complication known as the Jarisch-Herxheimer reaction, which is an acute febrile reaction within the first 24 hours of treatment. Symptoms include fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation, and mild hypotension. Although the reaction occurs in 10 to 25% of patients overall, it is most common in the treatment of secondary
syphilis. Symptoms last for 12 to 24 hours and are usually self-limiting. Patients can be treated symptomatically with antipyretics. All patients receiving initial treatment should be counseled regarding this reaction and instructed to report any symptoms they may develop.
syphilis. Symptoms last for 12 to 24 hours and are usually self-limiting. Patients can be treated symptomatically with antipyretics. All patients receiving initial treatment should be counseled regarding this reaction and instructed to report any symptoms they may develop.
TABLE 6.5 Oral Penicillin Desensitization Protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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For nonpregnant patients who are allergic to penicillin and who refuse penicillin desensitization or if it is not available, other treatment options include doxycycline, tetracycline, macrolide, and ceftriaxone regimens, although data regarding their effectiveness are limited. Azithromycin should be used with caution because T. pallidum chromosomal mutations have been associated with azithromycin resistance and treatment failures have been documented.
Response to therapy should be monitored with clinical and serologic examination at 3, 6, and 12 months.1 The level of antibody decline depends on the stage of infection and the antibody titer before treatment. Early syphilis may result in a faster antibody decline than latent syphilis. Clinical significance is indicated with a four-fold change in titer (e.g., from 1:16 to 1:4). A repeat titer should be obtained before initiation of treatment because titers can increase dramatically over a few days. Failure of nontreponemal antibody titers to decrease four-fold at 6 months indicates probable treatment failure or possible reinfection in primary or secondary syphilis. These patients should also be tested for HIV. However, in patients with high titers pretreatment (greater than 1:32), an observed decline may take 12 to 24 months, so as long as the titer is not rising, follow-up should be conservative. For patients with latent syphilis, an additional antibody titer should be performed at 24 months posttreatment. Titers should decline at least four-fold by 12 to 24 months after treatment. However, 15% of patients do not meet criterion for serologic cure 12 months after appropriate treatment and may remain “serofast.” A serofast state occurs when a patient’s nontreponemal titers persist at low levels (e.g., 1:2) even with appropriate therapy. The mechanism for this phenomenon is unknown. Periodic rechecking of titers in serofast patients is recommended. If follow-up cannot be ensured, retreatment and consideration of CSF examination may be considered. Additionally, all serofast patients should be tested for HIV infection as a potential cause of antibody deficiency. A four-fold rise in the antibody titer (e.g., 1:4 to 1:16) would indicate reinfection and retreatment with benzathine penicillin (2.4 million units IM weekly for 3 weeks) is recommended.
Sexual partners should also be evaluated and treated for infection according to recommendations by the CDC.1 Presumptive treatment is recommended for sexual partners who were exposed within 90 days preceding a diagnosis even if they are seronegative or if they are exposed after 90 days and no serologic testing or follow-up is available. For purposes of partner notification and presumptive treatment, the CDC recommends that patients with an unknown duration of syphilis who have high nontreponemal titers (e.g., greater than 1:32) can be assumed to have early syphilis. For long-term partners of patients with latent syphilis, clinical and serologic evaluations of the partner(s) should be done to guide treatment.
Cardiovascular syphilis can be treated with benzathine penicillin G 2.4 million units IM once weekly for 3 weeks. Although therapy does not reverse the cardiovascular complications associated with syphilis, it may delay disease progression. Recommended doses of benzathine penicillin are not detectable in CSF; therefore, intravenous penicillin G is recommended for the treatment of neurosyphilis. Intravenous penicillin G (3 to 4 million units IV every 4 hours or 18 to 24 million units every 24 hours by continuous infusion for 10 to 14 days) should be administered to the following:
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