Sexually Transmitted Diseases Treatment Guidelines, 2006

Prepared by
Kimberly A. Workowski, MD
Stuart M. Berman, MD
Division of STD Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)

The material in this report originated in National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), Kevin A. Fenton, MD, PhD, Director; and the Division of STD Prevention, John M. Douglas, MD, Director.

Corresponding preparer: Kimberly A. Workowski, MD, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 10 Corporate Square, Corporate Square Blvd., MS E-02, Atlanta, GA 30333. Telephone: 404-639-1898; Fax: 404-639-8610; E-mail: kgw2@cdc.gov.

Summary

These guidelines for the treatment of persons who have sexually transmitted diseases (STDs) were developed by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta, Georgia, during April 19--21, 2005. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2002 (MMWR 2002;51[No. RR-6]). Included in these updated guidelines are an expanded diagnostic evaluation for cervicitis and trichomoniasis; new antimicrobial recommendations for trichomoniasis; additional data on the clinical efficacy of azithromycin for chlamydial infections in pregnancy; discussion of the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; emergence of lymphogranuloma venereum proctocolitis among men who have sex with men (MSM); expanded discussion of the criteria for spinal fluid examination to evaluate for neurosyphilis; the emergence of azithromycin- resistant Treponema pallidum; increasing prevalence of quinolone-resistant Neisseria gonorrhoeae in MSM; revised discussion concerning the sexual transmission of hepatitis C; postexposure prophylaxis after sexual assault; and an expanded discussion of STD prevention approaches.

Introduction

Physicians and other health-care providers play a critical role in preventing and treating sexually transmitted diseases (STDs). These guidelines for the treatment of STDs are intended to assist with that effort. Although these guidelines emphasize treatment, prevention strategies and diagnostic recommendations also are discussed.

Methods

This report was produced through a multistage process. Beginning in 2004, CDC personnel and professionals knowledgeable in the field of STDs systematically reviewed evidence, including published abstracts and peer-reviewed journal articles concerning each of the major STDs, focusing on information that had become available since publication of the Sexually Transmitted Diseases Treatment Guidelines, 2002 (1). Background papers were written and tables of evidence were constructed summarizing the type of study (e.g., randomized controlled trial or case series), study population and setting, treatments or other interventions, outcome measures assessed, reported findings, and weaknesses and biases in study design and analysis. A draft document was developed on the basis of the reviews.

In April 2005, CDC staff members and invited consultants assembled in Atlanta, Georgia, for a 3-day meeting to present the key questions regarding STD treatment that emerged from the evidence-based reviews and the information available to answer those questions. When relevant, the questions focused on four principal outcomes of STD therapy for each individual disease: 1) microbiologic cure, 2) alleviation of signs and symptoms, 3) prevention of sequelae, and 4) prevention of transmission. Cost-effectiveness and other advantages (e.g., single-dose formulations and directly observed therapy of specific regimens) also were discussed. The consultants then assessed whether the questions identified were relevant, ranked them in order of priority, and attempted to arrive at answers using the available evidence. In addition, the consultants evaluated the quality of evidence supporting the answers on the basis of the number, type, and quality of the studies.

In several areas, the process diverged from that previously described. The sections on hepatitis B virus (HBV) and hepatitis A virus (HAV) infections are based on previously or recently approved recommendations (2--4) of the Advisory Committee on Immunization Practices. The recommendations for STD screening during pregnancy were developed after CDC staff reviewed the recommendations from other knowledgeable groups.

Throughout this report, the evidence used as the basis for specific recommendations is discussed briefly. More comprehensive, annotated discussions of such evidence will appear in background papers that will be published in a supplement issue of Clinical Infectious Diseases. When more than one therapeutic regimen is recommended, the sequence is in alphabetical order unless the choices for therapy are prioritized based on efficacy, convenience, or cost. For STDs with more than one recommended treatment regimen, it can be assumed that all regimens have similar efficacy and similar rates of intolerance or toxicity, unless otherwise specified. Persons treating STDs should use recommended regimens primarily; alternative regimens can be considered in instances of substantial drug allergy or other contraindications to the recommended regimens.

These recommendations were developed in consultation with public and private sector professionals knowledgeable in the treatment of persons with STDs (see Consultants list). The recommendations are applicable to various patient-care settings, including family planning clinics, private physicians' offices, managed care organizations, and other primary-care facilities.

These recommendations are meant to serve as a source of clinical guidance: health-care providers should always consider the individual clinical circumstances of each person in the context of local disease prevalence. These guidelines focus on the treatment and counseling of individual persons and do not address other community services and interventions that are important in STD/human immunodeficiency virus (HIV) prevention.

Clinical Prevention Guidance

The prevention and control of STDs are based on the following five major strategies: 1) education and counseling of persons at risk on ways to avoid STDs through changes in sexual behaviors; 2) identification of asymptomatically infected persons and of symptomatic persons unlikely to seek diagnostic and treatment services; 3) effective diagnosis and treatment of infected persons; 4) evaluation, treatment, and counseling of sex partners of persons who are infected with an STD; and 5) preexposure vaccination of persons at risk for vaccine-preventable STD.

Primary prevention of STD begins with changing the sexual behaviors that place persons at risk for infection. Health-care providers have a unique opportunity to provide education and counseling to their patients. As part of the clinical interview, health-care providers should routinely and regularly obtain sexual histories from their patients and address management of risk reduction as indicated in this report. Guidance in obtaining a sexual history is available in Contraceptive Technology, 18th edition (5) and in the curriculum provided by CDC's STD/HIV Prevention Training Centers (http://www.stdhivpreventiontraining.org). Counseling skills, characterized by respect, compassion, and a nonjudgmental attitude toward all patients, are essential to obtaining a thorough sexual history and to delivering prevention messages effectively. Key techniques that can be effective in facilitating rapport with patients include the use of 1) open-ended questions (e.g., "Tell me about any new sex partners you've had since your last visit" and "what's your experience with using condoms been like?"), 2) understandable language ("have you ever had a sore or scab on your penis?"), and 3) normalizing language ("some of my patients have difficulty using a condom with every sex act. How is it for you?"). One approach to eliciting information concerning five key areas of interest has been summarized.

The Five Ps: Partners, Prevention of Pregnancy, Protection from STDs, Practices, Past History of STDs

1. Partners

• "Do you have sex with men, women, or both?"
• "In the past 2 months, how many partners have you had sex with?"
• "In the past 12 months, how many partners have you had sex with?"

• "Are you or your partner trying to get pregnant?" If no, "What are you doing to prevent pregnancy?"

• "What do you do to protect yourself from STDs and HIV?"

• "To understand your risks for STDs, I need to understand the kind of sex you have had recently."
• "Have you had vaginal sex, meaning `penis in vagina sex'"?
• If yes, "Do you use condoms: never, sometimes, or always?"
• "Have you had anal sex, meaning `penis in rectum/anus sex'"?
• If yes, "Do you use condoms: never, sometimes, or always?"
• "Have you had oral sex, meaning `mouth on penis/vagina'"?

For condom answers

• If "never:" "Why don't you use condoms?"
• If "sometimes": "In what situations or with whom, do you not use condoms?"

• "Have you ever had an STD?"
• "Have any of your partners had an STD?"

Additional questions to identify HIV and hepatitis risk

• "Have you or any of your partners ever injected drugs?
• "Have any of your partners exchanged money or drugs for sex?"
• "Is there anything else about your sexual practices that I need to know about?"

Patients should be reassured that treatment will be provided regardless of individual circumstances (e.g., ability to pay, citizenship or immigration status, language spoken, or specific sex practices). Many patients seeking treatment or screening for a particular STD should be evaluated for all common STDs; even so, all patients should be informed concerning all the STDs for which they are being tested and if testing for a common STD (e.g., genital herpes) is not being performed.

STD/HIV Prevention Counseling

Effective delivery of prevention messages requires that providers integrate communication of general risk reduction messages that are relevant to the client (i.e., client-centered counseling) and education regarding specific actions that can reduce the risk for STD/HIV transmission (e.g., abstinence, condom use, limiting the number of sex partners, modifying sexual behaviors, and vaccination). Each of these specific actions is discussed separately in this report.

• Interactive counseling approaches directed at a patient's personal risk, the situations in which risk occurs, and the use of goal-setting strategies are effective in STD/HIV prevention (6). One such approach, client-centered STD/HIV prevention counseling, involves tailoring a discussion of risk reduction to the patient's individual situation. Client-centered counseling can have a beneficial effect on the likelihood of patients using risk-reduction practices and can reduce the risk for future acquisition of an STD. One effective client-centered approach is Project RESPECT, which demonstrated that a brief counseling intervention was associated with a reduced frequency of STD/HIV risk-related behaviors and with a lowered acquisition of STDs (7,8). Practice models based on Project RESPECT have been successfully implemented in clinic-based settings. Other approaches use motivational interviewing to move clients toward achievable risk reduction goals. CDC provides additional information on these and other effective behavioral interventions at http://effectiveinterventions.org.
• Interactive counseling can be used effectively by all health-care providers or can be conducted by specially trained counselors. The quality of counseling is best ensured when providers receive basic training in prevention counseling methods and skill-building approaches, periodic observation of counseling with immediate feedback by persons with expertise in the counseling approach, periodic counselor and/or patient satisfaction evaluations, and availability of expert assistance or referral for challenging situations. Training in client-centered counseling is available through the CDC STD/HIV Prevention Training Centers (http://www.stdhivpreventiontraining.org). Prevention counseling is most effective if provided in a nonjudgmental manner appropriate to the patient's culture, language, sex, sexual orientation, age, and developmental level.

In addition to individual prevention counseling, some videos and large group presentations provide explicit information concerning how to use condoms correctly. These have been effective in reducing the occurrence of additional STDs among persons at high risk, including STD clinic patients and adolescents.

Because the incidence of some STDs, notably syphilis, has increased in HIV-infected persons, the use of client-centered STD counseling for HIV-infected persons has received strong emphasis from public health agencies and organizations. Consensus guidelines issued by CDC, the Health Resources and Services Administration, the HIV Medicine Association of the Infectious Diseases Society of America, and the National Institutes of Health emphasize that STD/HIV risk assessment, STD screening, and client-centered risk reduction counseling should be provided routinely to HIV-infected persons (9). Several specific methods have been designed for the HIV care setting (10--12). Additional information regarding these approaches is available at http://effectiveinterventions.org.

Prevention Methods

Client-Initiated Interventions to Reduce Sexual Transmission of STD/HIV and Unintended Pregnancy

Abstinence and Reduction of Number of Sex Partners

The most reliable way to avoid transmission of STDs is to abstain from sex (i.e., oral, vaginal, or anal sex) or to be in a long-term, mutually monogamous relationship with an uninfected partner. Counseling that encourages abstinence from sexual intercourse is crucial for persons who are being treated for an STD (or whose partners are undergoing treatment) and for persons who want to avoid the possible consequences of sex completely (e.g., STD/HIV and unintended pregnancy). A more comprehensive discussion of abstinence is available in Contraceptive Technology, 18th edition (5). For persons embarking on a mutually monogamous relationship, screening for common STDs before initiating sex might reduce the risk for future transmission of asymptomatic STDs.

Preexposure Vaccination

Preexposure vaccination is one of the most effective methods for preventing transmission of some STDs. For example, because HBV infection is frequently sexually transmitted, hepatitis B vaccination is recommended for all unvaccinated, uninfected persons being evaluated for an STD. In addition, hepatitis A vaccine is licensed and is recommended for men who have sex with men (MSM) and illicit drug users (i.e., both injecting and noninjecting). Specific details regarding hepatitis A and B vaccination are available at http://www.cdc.gov/hepatitis. A quadrivalent vaccine against human papillomavirus (HPV types 6, 11, 16, 18) is now available and licensed for females aged 9--26 years. Vaccine trials for other STDs are being conducted.

Male Condoms

When used consistently and correctly, male latex condoms are highly effective in preventing the sexual transmission of HIV infection (i.e., HIV-negative partners in heterosexual serodiscordant relationships in which condoms were consistently used were 80% less likely to become HIV-infected compared with persons in similar relationships in which condoms were not used) and can reduce the risk for other STDs, including chlamydia, gonorrhea, and trichomoniasis, and might reduce the risk of women developing pelvic inflammatory disease (PID) (13,14). Condom use might reduce the risk for transmission of herpes simplex virus-2 (HSV-2), although data for this effect are more limited (15,16). Condom use might reduce the risk for HPV-associated diseases (e.g., genital warts and cervical cancer [17]) and mitigate the adverse consequences of infection with HPV, as their use has been associated with higher rates of regression of cervical intraepithelial neoplasia (CIN) and clearance of HPV infection in women (18), and with regression of HPV-associated penile lesions in men (19). A limited number of prospective studies have demonstrated a protective effect of condoms on the acquisition of genital HPV; one recent prospective study among newly sexually active college women demonstrated that consistent condom use was associated with a 70% reduction in risk for HPV transmission (20).

Condoms are regulated as medical devices and are subject to random sampling and testing by the Food and Drug Administration (FDA). Each latex condom manufactured in the United States is tested electronically for holes before packaging. Rates of condom breakage during sexual intercourse and withdrawal are approximately two broken condoms per 100 condoms used in the United States. The failure of condoms to protect against STD transmission or unintended pregnancy usually results from inconsistent or incorrect use rather than condom breakage.

Male condoms made of materials other than latex are available in the United States. Although they have had higher breakage and slippage rates when compared with latex condoms and are usually more costly, the pregnancy rates among women whose partners use these condoms are similar to latex condoms. Two general categories of nonlatex condoms exist. The first type is made of polyurethane or other synthetic material and provides protection against STD/HIV and pregnancy equal to that of latex condoms. These can be substituted for persons with latex allergy. The second type is natural membrane condoms (frequently called "natural" condoms or, incorrectly, lambskin condoms). These condoms are usually made from lamb cecum and can have pores up to 1500 nm in diameter. Whereas these pores do not allow the passage of sperm, they are more than 10 times the diameter of HIV and more than 25 times that of HBV. Moreover, laboratory studies demonstrate that viral STD transmission can occur with natural membrane condoms. Using natural membrane condoms for protection against STDs is not recommended.

Patients should be advised that condoms must be used consistently and correctly to be effective in preventing STDs, and they should be instructed in the correct use of condoms. The following recommendations ensure the proper use of male condoms:

• Use a new condom with each sex act (e.g., oral, vaginal, and anal).
• Carefully handle the condom to avoid damaging it with fingernails, teeth, or other sharp objects.
• Put the condom on after the penis is erect and before any genital, oral, or anal contact with the partner.
• Use only water-based lubricants (e.g., K-Y Jelly™, Astroglide™, AquaLube™, and glycerin) with latex condoms. Oil-based lubricants (e.g., petroleum jelly, shortening, mineral oil, massage oils, body lotions, and cooking oil) can weaken latex.
• Ensure adequate lubrication during vaginal and anal sex, which might require the use of exogenous water-based lubricants.
• To prevent the condom from slipping off, hold the condom firmly against the base of the penis during withdrawal, and withdraw while the penis is still erect.

Female Condoms

Laboratory studies indicate that the female condom (Reality™), which consists of a lubricated polyurethane sheath with a ring on each end that is inserted into the vagina, is an effective mechanical barrier to viruses, including HIV, and to semen (21). A limited number of clinical studies have evaluated the efficacy of female condoms in providing protection from STDs, including HIV (22). If used consistently and correctly, the female condom might substantially reduce the risk for STDs. When a male condom cannot be used properly, sex partners should consider using a female condom. Female condoms are costly compared with male condoms. The female condom also has been used for STD/HIV protection during receptive anal intercourse (23). Whereas it might provide some protection in this setting, its efficacy is undefined.

Vaginal Spermicides and Diaphragms

Vaginal spermicides containing nonoxynol-9 (N-9) are not effective in preventing cervical gonorrhea, chlamydia, or HIV infection (24). Furthermore, frequent use of spermicides containing N-9 has been associated with disruption of the genital epithelium, which might be associated with an increased risk for HIV transmission. Therefore, N-9 is not recommended for STD/HIV prevention. In case-control and cross-sectional studies, diaphragm use has been demonstrated to protect against cervical gonorrhea, chlamydia, and trichomoniasis; a randomized controlled trial will be conducted. On the basis of all available evidence, diaphragms should not be relied on as the sole source of protection against HIV infection. Diaphragm and spermicide use have been associated with an increased risk for bacterial urinary tract infections in women.

Condoms and N-9 Vaginal Spermicides

Condoms lubricated with spermicides are no more effective than other lubricated condoms in protecting against the transmission of HIV and other STDs, and those that are lubricated with N-9 pose the concerns that have been previously discussed. Use of condoms lubricated with N-9 is not recommended for STD/HIV prevention because spermicide-coated condoms cost more, have a shorter shelf-life than other lubricated condoms, and have been associated with urinary tract infection in young women.

Rectal Use of N-9 Spermicides

Recent studies indicate that N-9 might increase the risk for HIV transmission during vaginal intercourse (24). Although similar studies have not been conducted among men who use N-9 spermicide during anal intercourse with other men, N-9 can damage the cells lining the rectum, which might provide a portal of entry for HIV and other sexually transmissible agents. Therefore, N-9 should not be used as a microbicide or lubricant during anal intercourse.

Nonbarrier Contraception, Surgical Sterilization, and Hysterectomy

Sexually active women who are not at risk for pregnancy might incorrectly perceive themselves to be at no risk for STDs, including HIV infection. Contraceptive methods that are not mechanical barriers offer no protection against HIV or other STDs. Women who use hormonal contraception (e.g., oral contraceptives, Norplant™, and Depo-Provera™), have intrauterine devices (IUD), have been surgically sterilized, or have had hysterectomies should be counseled regarding the use of condoms and the risk for STDs, including HIV infection.

Emergency Contraception (EC)

Emergency use of oral contraceptive pills containing levonorgesterol alone reduces the risk for pregnancy after unprotected intercourse by 89%. Pills containing a combination of ethinyl estradiol and either norgestrel or levonorgestrel can be used and reduce the risk for pregnancy by 75%. Emergency insertion of a copper IUD also is highly effective, reducing the risk by as much as 99%. EC with oral contraceptive pills should be initiated as soon as possible after unprotected intercourse and definitely within 120 hours (i.e., 5 days). The only medical contraindication to provision of EC is current pregnancy.

Providers who manage persons at risk for STDs should counsel women concerning the option for EC, if indicated, and provide it in a timely fashion if desired by the woman. Plan B (two 750 mcg levonorgestrel tablets) has been approved by FDA and is available in the United States for the prevention of unintended pregnancy. Additional information on EC is available in Contraceptive Technology, 18th edition (5), or at http://www.arhp.org/healthcareproviders/resources/contraceptionresources.

Postexposure Prophylaxis (PEP) for HIV

Guidelines for the use of PEP aimed at preventing HIV acquisition as a result of sexual exposure are available and are discussed in this report (see Sexual Assault and STDs).

Partner Management

Partner notification, previously referred to as "contact tracing" but recently included in the broader category of partner services, is the process by which providers or public health authorities learn from persons with STDs about their sex partners and help to arrange for the evaluation and treatment of sex partners. Providers can seek this information and help to arrange for evaluation and treatment of sex partners, either directly or with assistance from state and local health departments. The intensity of partner services and the specific STDs for which they are offered vary among providers, agencies, and geographic areas. Ideally, such services should be accompanied by health counseling and might include referral of patients and their partners for other services, whenever appropriate.

In general, whether partner notification effectively decreases exposure to STDs and whether it changes the incidence and prevalence of STDs in a community are uncertain. The paucity of supporting evidence regarding the effectiveness of partner notification has spurred the exploration of alternative approaches. One such approach is to place partner notification in a larger context by making interventions in the sexual and social networks in which persons are exposed to STDs. Prospective evaluations incorporating assessment of venues, community structure, and social and sexual, contacts in conjunction with partner notification of efforts are promising in terms of increasing case-finding and warrant further exploration. The scope of such efforts probably precludes individual clinician efforts to use network-based approaches, but STD-control programs might find them useful.

Many persons individually benefit from partner notification. When partners are treated, index patients have reduced risk for reinfection. At a population level, partner notification can disrupt networks of STD transmission and reduce disease incidence. Therefore, providers should encourage their patients with STDs to notify their sex partners and urge them to seek medical evaluation and treatment, regardless of whether assistance is available from health agencies. When medical evaluation, counseling, and treatment of partners cannot be done because of the particular circumstances of a patient or partner or because of resource limitations, other partner management options can be considered. One option is patient-delivered therapy, a form of expedited partner therapy (EPT) in which partners of infected patients are treated without previous medical evaluation or prevention counseling (http://www.cdc.gov/std/treatment/EPTFinalReport2006.pdf). The evidence supporting patient-delivered therapy is based on three clinical trials that included heterosexual men and women with chlamydia or gonorrhea. The strength of the supporting evidence differed by STD and by the sex of the index case when reinfection of the index case was the measured outcome (25--27). Despite this variation, patient-delivered therapy (i.e., via medications or prescriptions) can prevent reinfection of index case and has been associated with a higher likelihood of partner notification, compared with unassisted patient referral of partners. Medications and prescriptions for patient-delivered therapy should be accompanied by treatment instructions, appropriate warnings about taking medications if pregnant, general health counseling, and advice that partners should seek personal medical evaluations, particularly women with symptoms of STDs or PID. Existing data suggest that EPT has a limited role in partner management for trichomoniasis (28). No data support its use in the routine management of syphilis. There is no experience with expedited partner therapy for gonorrhea or chlamydia infection among MSM. Currently, EPT is not feasible in many settings because of operational barriers, including the lack of clear legal status of EPT in some states.

Reporting and Confidentiality

The accurate and timely reporting of STDs is integrally important for assessing morbidity trends, targeting limited resources, and assisting local health authorities in partner notification and treatment. STD/HIV and acquired immunodeficiency syndrome (AIDS) cases should be reported in accordance with state and local statutory requirements. Syphilis, gonorrhea, chlamydia, chanroid, HIV infection, and AIDS are reportable diseases in every state. The requirements for reporting other STDs differ by state, and clinicians should be familiar with state and local reporting requirements.

Reporting can be provider- and/or laboratory-based. Clinicians who are unsure of state and local reporting requirements should seek advice from state or local health departments or STD programs. STD and HIV reports are kept strictly confidential. In the majority of jurisdictions, such reports are protected by statute from subpoena. Before public health representatives conduct a follow-up of a positive STD-test result, they should consult the patient's health-care provider to verify the diagnosis and treatment.

Special Populations

Pregnant Women

Intrauterine or perinatally transmitted STDs can have severely debilitating effects on pregnant women, their partners, and their fetuses. All pregnant women and their sex partners should be asked about STDs, counseled about the possibility of perinatal infections, and ensured access to treatment, if needed.

Recommended Screening Tests

• All pregnant women in the United States should be tested for HIV infection as early in pregnancy as possible. Testing should be conducted after the woman is notified that she will be tested for HIV as part of the routine panel of prenatal tests, unless she declines the test (i.e., opt-out screening). For women who decline HIV testing, providers should address their objections, and where appropriate, continue to strongly encourage testing. Women who decline testing because they have had a previous negative HIV test should be informed of the importance of retesting during each pregnancy. Testing pregnant women is vital not only to maintain the health of the patient but also because interventions (i.e., antiretroviral and obstetrical) are available that can reduce perinatal transmission of HIV. Retesting in the third trimester (i.e., preferably before 36 weeks' gestation) is recommended for women at high risk for acquiring HIV infection (i.e., women who use illicit drugs, have STDs during pregnancy, have multiple sex partners during pregnancy, or have HIV-infected partners). Rapid HIV testing should be performed on women in labor with undocumented HIV status. If a rapid HIV test result is positive, antiretroviral prophylaxis (with consent) should be administered without waiting for the results of the confirmatory test.
• A serologic test for syphilis should be performed on all pregnant women at the first prenatal visit. In populations in which use of prenatal care is not optimal, rapid plasma reagin (RPR) card test screening (and treatment, if that test is reactive) should be performed at the time a pregnancy is confirmed. Women who are at high risk for syphilis, live in areas of high syphilis morbidity, are previously untested, or have positive serology in the first trimester should be screened again early in the third trimester (28 weeks' gestation) and at delivery. Some states require all women to be screened at delivery. Infants should not be discharged from the hospital unless the syphilis serologic status of the mother has been determined at least one time during pregnancy and preferably again at delivery. Any woman who delivers a stillborn infant should be tested for syphilis.
• All pregnant women should be routinely tested for hepatitis B surface antigen (HBsAg) during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been previously vaccinated or tested. Women who were not screened prenatally, those who engage in behaviors that put them at high risk for infection (e.g., more than one sex partner in the previous 6 months, evaluation or treatment for an STD, recent or current injecting-drug use, and HBsAg-positive sex partner), and those with clinical hepatitis should be retested at the time of admission to the hospital for delivery. Women at risk for HBV infection also should be vaccinated. To avoid misinterpreting a transient positive HBsAg result during the 21 days after vaccination, HBsAg testing should be performed before the vaccination.
• All laboratories that conduct HBsAg tests should use an HBsAg test that is FDA-cleared and should perform testing according to the manufacturer's labeling, including testing of initially reactive specimens with a licensed neutralizing confirmatory test. When pregnant women are tested for HBsAg at the time of admission for delivery, shortened testing protocols may be used, and initially reactive results should prompt expedited administration of immunoprophylaxis to infants.
• All pregnant women should be routinely tested for Chlamydia trachomatis (see Chlamydia Infections, Diagnostic Considerations) at the first prenatal visit. Women aged <25 years and those at increased risk for chlamydia (i.e., women who have a new or more than one sex partner) also should be retested during the third trimester to prevent maternal postnatal complications and chlamydial infection in the infant. Screening during the first trimester might prevent the adverse effects of chlamydia during pregnancy, but supportive evidence for this is lacking. If screening is performed only during the first trimester, a longer period exists for acquiring infection before delivery.
• All pregnant women at risk for gonorrhea or living in an area in which the prevalence of Neisseria gonorrhoeae is high should be tested at the first prenatal visit for N. gonorrhoeae. (See Gonococcal Infections, Diagnostic Considerations). A repeat test should be performed during the third trimester for those at continued risk.
• All pregnant women at high risk for hepatitis C infection should be tested for hepatitis C antibodies (see Hepatitis C, Diagnostic Considerations) at the first prenatal visit. Women at high risk include those with a history of injecting-drug use and those with a history of blood transfusion or organ transplantion before 1992.
• Evaluation for bacterial vaginosis (BV) might be conducted during the first prenatal visit for asymptomatic patients who are at high risk for preterm labor (e.g., those who have a history of a previous preterm delivery). Evidence does not support routine testing for BV.
• A Papanicolaou (Pap) smear should be obtained at the first prenatal visit if none has been documented during the preceding year.

Other Concerns

• Women who are HBsAg positive should be reported to the local and/or state health department to ensure that they are entered into a case-management system and that timely and appropriate prophylaxis is provided for their infants. Information concerning the pregnant woman's HBsAg status should be provided to the hospital in which delivery is planned and to the health-care provider who will care for the newborn. In addition, household and sex contacts of women who are HBsAg positive should be vaccinated.
• Women who are HBsAg positive should be provided with, or referred for, appropriate counseling and medical management. Pregnant women who are HBsAg positive pregnant women should receive information regarding hepatitis B that addresses
  --- modes of transmission;
  --- perinatal concerns (e.g., breastfeeding is not contraindicated);
  --- prevention of HBV transmission, including the importance of postexposure prophylaxis for the newborn infant and hepatitis B vaccination for household contacts and sex partners; and
  --- evaluation for and treatment of chronic HBV infection.
• No treatment is available for HCV-infected pregnant women. However, all women with HCV infection should receive appropriate counseling and supportive care as needed (see Hepatitis C, Prevention). No vaccine is available to prevent HCV transmission.
• In the absence of lesions during the third trimester, routine serial cultures for HSV are not indicated for women who have a history of recurrent genital herpes. Prophylactic cesarean section is not indicated for women who do not have active genital lesions at the time of delivery. In addition, insufficient evidence exists to recommend routine HSV-2 serologic screening among previously undiagnosed women during pregnancy, nor does sufficient evidence exist to recommend routine antiviral suppressive therapy late in gestation for all HSV-2 positive women.
• The presence of genital warts is not an indication for cesarean section.
• Not enough evidence exists to recommend routine screening for Trichomonas vaginalis in asymptomatic pregnant women.

For a more detailed discussion of STD testing and treatment among pregnant women and other infections not transmitted sexually, refer to the following references: Guide to Clinical Preventive Services (29); Guidelines for Perinatal Care (30); ACOG Practice Bulletin: Prophylatic Antibiotics in Labor and Delivery (31); ACOG Committee Opinion: Primary and Preventive Care: Periodic Assessments (32); Recommendations for the Prevention and Management of Chlamydia trachomatis Infections (33); Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States---Recommendations of the Immunization Practices Advisory Committee (ACIP) (2,4); Mother-To-Infant Transmission of Hepatitis C Virus (34); Hepatitis C: Screening in Pregnancy (35); American College of Obstetricians and Gynecologists (ACOG) Educational Bulletin: Viral Hepatitis in Pregnancy (36); Revised Public Health Service Recommendations for HIV Screening of Pregnant Women (37); Prenatal and Perinatal Human Immunodeficiency Virus Testing: Expanded Recommendations (38); US Preventative Task Force HIV Screening Guidelines (39); Rapid HIV Antibody Testing During Labor and Delivery for Women of Unknown HIV Status: A Practical Guide and Model Protocol (40); and Sexually Transmitted Diseases in Adolescents (41).

These sources are not entirely consistent in their recommendations. For example, the Guide to Clinical Preventive Services recommends screening of patients at high risk for chlamydia but indicates that the optimal timing for screening is uncertain. The Guidelines for Perinatal Care recommends that pregnant women at high risk for chlamydia be screened for infection during the first prenatal care visit and during the third trimester. Recommendations to screen pregnant women for STDs are based on disease severity and sequelae, prevalence in the population, costs, medicolegal considerations (e.g., state laws), and other factors. The screening recommendations in this report are broader (i.e., if followed, more women will be screened for more STDs than would be screened by following other recommendations) and are compatible with other CDC guidelines.

Adolescents

The rates of many STDs are highest among adolescents. For example, the reported rates of chlamydia and gonorrhea are highest among females aged 15--19 years, and many persons acquire HPV infection during their adolescent years. Among adolescents with acute HBV infection, the most commonly reported risk factors are having sexual contact with a chronically infected person or with multiple sex partners, or reporting their sexual preference as homosexual. As part of a comprehensive strategy to eliminate HBV transmission in the United States, ACIP has recommended that all children and adolescents be administered HBV vaccine (2).

Younger adolescents (i.e., persons aged <15 years) who are sexually active are at particular risk for STDs, especially youth in detention facilities, STD clinic patients, male homosexuals, and injecting-drug users (IDUs). Adolescents are at higher risk for STDs because they frequently have unprotected intercourse, are biologically more susceptible to infection, are engaged in sexual partnerships frequently of limited duration, and face multiple obstacles to using health care. Several of these issues can be addressed by clinicians who provide services to adolescents. Clinicians can address adolescents' lack of knowledge and awareness regarding the risks and consequences of STDs by offering guidance concerning healthy sexual behavior and, therefore, prevent the establishment of patterns of behavior that can undermine sexual health.

With a few exceptions, all adolescents in the United States can legally consent to the confidential diagnosis and treatment of STDs. In all 50 states and the District of Columbia, medical care for STDs can be provided to adolescents without parental consent or knowledge. In addition, in the majority of states, adolescents can consent to HIV counseling and testing. Consent laws for vaccination of adolescents differ by state. Several states consider provision of vaccine similar to treatment of STDs and provide vaccination services without parental consent. Because of the crucial importance of confidentially, health-care providers should follow policies that provide confidentiality and comply with state laws for STD services.

Despite the prevalence of STDs among adolescents, providers frequently fail to inquire about sexual behavior, assess risk for STDs, provide counseling on risk reduction, and screen for asymptomatic infection during clinical encounters. The style and content of counseling and health education on these sensitive subjects should be adapted for adolescents. Discussions should be appropriate for the patient's developmental level and should be aimed at identifying risky behaviors (e.g., sex and drug-use behaviors). Careful, nonjudgmental, and thorough counseling are particularly vital for adolescents who might not acknowledge that they engage in high-risk behaviors.

Children

Management of children who have STDs requires close cooperation between clinicians, laboratorians, and child-protection authorities. Official investigations, when indicated, should be initiated promptly. Some diseases (e.g., gonorrhea, syphilis, and chlamydia), if acquired after the neonatal period, are virtually 100% indicative of sexual contact. For other diseases (e.g., HPV infection and vaginitis), the association with sexual contact is not as clear (see Sexual Assault and STDs).

MSM

Some MSM are at high risk for HIV infection and other viral and bacterial STDs. The frequency of unsafe sexual practices and the reported rates of bacterial STDs and incident HIV infection have declined substantially in MSM from the 1980s through the mid-1990s. However, during the previous 10 years, increased rates of infectious syphilis, gonorrhea, and chlamydial infection and of higher rates of unsafe sexual behaviors have been documented among MSM in the United States and virtually all industrialized countries. The effect of these behavioral changes on HIV transmission has not been ascertained, but preliminary data suggest that the incidence of HIV infection might be increasing among some MSM. These adverse trends probably are related to changing attitudes concerning HIV infection because of the effects of improved HIV/AIDS therapy on quality of life and survival, changing patterns of substance abuse, demographic shifts in MSM populations, and changes in sex partner networks resulting from new venues for partner acquisition.

Clinicians should assess the risks of STDs for all male patients, including a routine inquiry about the sex of patients' sex partners. MSM, including those with HIV infection, should routinely undergo nonjudgmental STD/HIV risk assessment and client-centered prevention counseling to reduce the likelihood of acquiring or transmitting HIV or other STDs. Clinicians should be familiar with local community resources available to assist MSM at high risk in facilitating behavioral change. Clinicians also should routinely ask sexually active MSM about symptoms consistent with common STDs, including urethral discharge, dysuria, genital and perianal ulcers, regional lymphadenopathy, skin rash, and anorectal symptoms consistent with proctitis. Clinicians also should maintain a low threshold for diagnostic testing of symptomatic patients.

Routine laboratory screening for common STDs is indicated for all sexually active MSM. The following screening recommendations are based on preliminary data (42,43). These tests should be performed at least annually for sexually active MSM, including men with or without established HIV infection:

• HIV serology, if HIV negative or not tested within the previous year;
• syphilis serology;
• a test for urethral infection with N. gonorrhoeae and C. trachomatis in men who have had insertive intercourse* during the preceding year;
• a test for rectal infection^† with N. gonorrhoeae and C. trachomatis in men who have had receptive anal intercourse* during the preceding year;
• a test for pharyngeal infection^† with N. gonorrhoeae in men who have acknowledged participation in receptive oral intercourse* during the preceding year; testing for C. trachomatis pharyngeal infection is not recommended.

In addition, some specialists would consider type-specific serologic tests for HSV-2, if infection status is unknown. Routine testing for anal cytologic abnormalities or anal HPV infection is not recommended until more data are available on the reliability of screening methods, the safety of and response to treatment, and programmatic considerations.

More frequent STD screening (i.e., at 3--6 month intervals) is indicated for MSM who have multiple or anonymous partners, have sex in conjunction with illicit drug use, use methamphetamine, or whose sex partners participate in these activities.

Vaccination against hepatitis A and B is recommended for all MSM in whom previous infection or immunization cannot be documented. Preimmunization serologic testing might be considered to reduce the cost of vaccinating MSM who are already immune to these infections, but this testing should not be delay vaccination. Vaccinating persons who are immune to HAV or HBV infection because of previous infection or vaccination does not increase the risk for vaccine-related adverse events (see Hepatitis B, Prevaccination Antibody Screening).

Women Who Have Sex with Women (WSW)

Few data are available on the risk of STDs conferred by sex between women, but transmission risk probably varies by the specific STD and sexual practice (e.g., oral-genital sex, vaginal or anal sex using hands, fingers, or penetrative sex items, and oral-anal sex) (44,45). Practices involving digital-vaginal or digital-anal contact, particularly with shared penetrative sex items, present a possible means for transmission of infected cervicovaginal secretions. This possibility is most directly supported by reports of metronidazole-resistant trichomoniasis and genotype-concordant HIV transmitted sexually between women who reported these behaviors and by the high prevalence of BV among monogamous WSW. Transmission of HPV can occur with skin-to-skin or skin-to-mucosa contact, which can occur during sex between women. HPV deoxyribonucleic acid (DNA) has been detected through polymerase chain reaction (PCR)-based methods from the cervix, vagina, and vulva in 13%--30% of WSW, and high- and low-grade squamous intraepithelial lesions (SIL) have been detected on Pap tests in WSW who reported no previous sex with men (46). However, the majority of self-identified WSW (53%--99%) have had sex with men and might continue this practice (47). Therefore, all women should undergo Pap test screening using current national guidelines, regardless of sexual preference or sexual practices.

HSV-2 genital transmission between female sex partners is probably inefficient, but the relatively frequent practice of orogenital sex among WSW might place them at higher risk for genital infection with HSV-1. This hypothesis is supported by the recognized association between HSV-1 seropositivity and previous number of female partners among WSW. Transmission of syphilis between female sex partners, probably through oral sex, has been reported. Although the rate of transmission of C. trachomatis between women is unknown, WSW who also have sex with men are at risk and should undergo routine screening according to guidelines.

HIV Infection: Detection, Counseling, and Referral

Infection with HIV produces a spectrum of disease that progresses from a clinically latent or asymptomatic state to AIDS as a late manifestation. The pace of disease progression varies. In untreated patients, the time between infection with HIV and the development of AIDS ranges from a few months to as long as 17 years (median: 10 years). The majority of adults and adolescents infected with HIV remain symptom-free for extended periods, but viral replication is active during all stages of infection and increases substantially as the immune system deteriorates. In the absence of treatment, AIDS will develop eventually in nearly all HIV-infected persons.

Improvements in antiretroviral therapy and increasing awareness among both patients and health-care providers of the risk factors associated with HIV transmission have led to more testing for HIV and earlier diagnosis, frequently before symptoms develop. However, the conditions of nearly 40% of persons who acquire HIV infection continue to be diagnosed late, within 1 year of acquiring AIDS. Prompt diagnosis of HIV infection is essential for multiple reasons. Treatments are available that slow the decline of immune system function; use of these therapies has been associated with substantial declines in HIV-associated morbidity and mortality in recent years. HIV-infected persons who have altered immune function are at increased risk for infections for which preventive measures are available (e.g., Pneumocystis jiroveci pneumonia, toxoplasma encephalitis [TE], disseminated Mycobacterium avium complex [MAC] disease, tuberculosis [TB], and bacterial pneumonia). Because of its effect on the immune system, HIV affects the diagnosis, evaluation, treatment, and follow-up of multiple other diseases and might affect the efficacy of antimicrobial therapy for some STDs. Finally, the early diagnosis of HIV enables health-care providers to counsel infected patients, refer them to various support services, and help prevent HIV transmission to others. Acutely infected persons might have elevated HIV viral loads and, therefore, might be more likely to transmit HIV to their partners (48,49).

Proper management of HIV infection involves a complex array of behavioral, psychosocial, and medical services. Although some services might not be available in STD treatment facilities. Therefore, referral to a health-care provider or facility experienced in caring for HIV-infected patients is advised. Providers working in STD-treatment facilities should be knowledgeable about the options for referral available in their communities. While receiving care in STD-treatment facilities, HIV-infected patients should be educated about HIV infection and the various options available for support services and HIV care.

A detailed discussion of the multiple, complex services required for management of HIV infection is beyond the scope of this section; however, this information is available in other published resources (6,9,50,51). In subsequent sections, this report provides information regarding diagnostic testing for HIV infection, counseling patients who have HIV infection, referral of patients for support services, including medical care, and the management of sex and injecting-drug partners in STD-treatment facilities. In addition, the report discusses HIV infection during pregnancy and in infants and children.

Detection of HIV Infection: Screening and Diagnostic Testing

All persons who seek evaluation and treatment for STDs should be screened for HIV infection. Screening should be routine, regardless of whether the patient is known or suspected to have specific behavioral risks for HIV infection.

Consent and Pretest Information

HIV screening should be voluntary and conducted only with the patient's knowledge and understanding that testing is planned. Persons should be informed orally or in writing that HIV testing will be performed unless they decline (i.e., opt-out screening). Oral or written communications should include an explanation of positive and negative test results, and patients should be offered an opportunity to ask questions and to decline testing.

Prevention Counseling

Prevention counseling does not need to be explicitly linked to the HIV-testing process. However, some patients might be more likely to think about HIV and consider their risks when undergoing an HIV test. HIV testing might present an ideal opportunity to provide or arrange for prevention counseling to assist with behavior changes that can reduce risk for acquiring HIV infection. Prevention counseling should be offered and encouraged in all health-care facilities serving patients at high risk and in those (e.g., STD clinics) where information on HIV-risk behaviors is routinely elicited.

Diagnostic Testing

HIV infection usually is diagnosed by tests for antibodies against HIV-1. Some combination tests also detect antibodies against HIV-2 (i.e., HIV-1/2). Antibody testing begins with a sensitive screening test (e.g., the enzyme immunoassay [EIA] or rapid test). The advent of HIV rapid testing has enabled clinicians to make a substantially accurate presumptive diagnosis of HIV-1 infection within half an hour. This testing can facilitate the identification of the more than 250,000 persons living with undiagnosed HIV in the United States. Reactive screening tests must be confirmed by a supplemental test (e.g., the Western blot [WB]) or an immunofluorescence assay (IFA) (52). If confirmed by a supplemental test, a positive antibody test result indicates that a person is infected with HIV and is capable of transmitting the virus to others. HIV antibody is detectable in at least 95% of patients within 3 months after infection. Although a negative antibody test result usually indicates that a person is not infected, antibody tests cannot exclude recent infection.

The majority of HIV infections in the United States are caused by HIV-1. However, HIV-2 infection should be suspected in persons who have epidemiologic risk factors, including being from West Africa (where HIV-2 is endemic) or have sex partners from endemic areas, have sex partners known to be infected with HIV-2, or have received a blood transfusion or nonsterile injection in a West African country. HIV-2 testing also is indicated when clinical evidence of HIV exists but tests for HIV-1 antibodies or HIV-1 viral load are not positive, or when HIV-1 WB results include the unusual indeterminate pattern of gag (p55, p24, p17) plus pol (p66, p51, p31) bands in the absence of env (gp160, gp120, gp41) bands.

Health-care providers should be knowledgeable about the symptoms and signs of acute retroviral syndrome, which is characterized by fever, malaise, lymphadenopathy, and skin rash. This syndrome frequently occurs in the first few weeks after HIV infection, before antibody test results become positive. Suspicion of acute retroviral syndrome should prompt nucleic acid testing (HIV plasma ribonucleic acid [RNA]) to detect the presence of HIV, although not all nucleic acid tests are approved for diagnostic purposes; a positive HIV nucleic acid test should be confirmed by subsequent antibody testing to document seroconversion (using standard methods, EIA, and WB). Acutely infected patients might be highly contagious because of increased plasma and genital HIV RNA concentrations and might be continuing to engage in risky behaviors (48,49). Current guidelines suggest that persons with recently acquired HIV infection might benefit from antiretroviral drugs and be candidates for clinical trials (53,54). Therefore, patients with acute HIV infection should be referred immediately to an HIV clinical care provider.

Diagnosis of HIV infection should prompt efforts to reduce the risk behavior that resulted in HIV infection and could result in transmission of HIV to others (55). Early counseling and education are particularly important for persons with recently acquired infection because HIV plasma RNA levels are characteristically high during this phase of infection and probably constitute an increased risk for HIV transmission. The following are specific recommendations for diagnostic testing for HIV infection:

• HIV screening is recommended for all persons who seek evaluation and treatment for STDs.
• HIV testing must be voluntary.
• Consent for HIV testing should be incorporated into the general consent for care (verbally or in writing) with an opportunity to decline (opt-out screening).
• HIV rapid testing must be considered, especially in clinics where a high proportion of patients do not return for HIV test results.
• Positive screening tests for HIV antibody must be confirmed by a supplemental test (e.g., WB or IFA) before being considered diagnostic of HIV infection.
• Persons who have positive HIV test results (screening and confirmatory) must receive initial HIV prevention counseling before leaving the testing site. Such persons should 1) receive a medical evaluation and, if indicated, behavioral and psychological services, or 2) be referred for these services.
• Providers should be alert to the possibility of acute retroviral syndrome and should perform nucleic acid testing for HIV, if indicated. Patients suspected of having recently acquired HIV infection should be referred for immediate consultation with a specialist.

Counseling for Patients with HIV Infection and Referral to Support Services

Persons can be expected to be distressed when first informed of a positive HIV test result. Such persons face multiple major adaptive challenges, including 1) accepting the possibility of a shortened life span, 2) coping with the reactions of others to a stigmatizing illness, 3) developing and adopting strategies for maintaining physical and emotional health, and 4) initiating changes in behavior to prevent HIV transmission to others. Many persons will require assistance with making reproductive choices, gaining access to health services, confronting possible employment or housing discrimination, and coping with changes in personal relationships. Therefore, behavioral and psychosocial services are an integral part of health care for HIV-infected persons. Such services should be available on site or through referral when HIV infection is diagnosed. A comprehensive discussion of specific recommendations is available in the Guidelines for HIV Counseling, Testing, and Referral and Revised Recommendations for HIV Screening of Pregnant Women (6). Innovative and successful interventions to decrease risk taking by HIV-infected patients have been developed for diverse populations (12).

Practice settings for offering HIV care differ depending on local resources and needs. Primary care providers and outpatient facilities should ensure that appropriate resources are available for each patient to avoid fragmentation of care. Although a single source that is capable of providing comprehensive care for all stages of HIV infection is preferred, the limited availability of such resources frequently results in the need to coordinate care among medical and social service providers in different locations. Providers should avoid long delays between diagnosis of HIV infection and access to additional medical and psychosocial services. The use of HIV rapid testing can help avoid unnecessary delays.

Recently identified HIV infection might not have been recently acquired. Persons newly diagnosed with HIV might be at any stage of infection. Therefore, health-care providers should be alert for symptoms or signs that suggest advanced HIV infection (e.g., fever, weight loss, diarrhea, cough, shortness of breath, and oral candidiasis). The presence of any of these symptoms should prompt urgent referral for specialty medical care. Similarly, providers should be alert for signs of psychologic distress and be prepared to refer patients accordingly.

Diagnosis of HIV infection reinforces the need to counsel patients regarding high-risk behaviors because the consequences of such behaviors include the risk for acquiring additional STDs and for transmitting HIV (and other STDs) to other persons. Such attention to behaviors in HIV-infected persons is consistent with national strategies for HIV prevention (55). Providers should refer patients for prevention counseling and risk-reduction support concerning high-risk behaviors (e.g., substance abuse and high-risk sexual behaviors). In multiple recent studies, researchers have developed successful prevention interventions for different HIV-infected populations that can be adapted to individuals (56,57).

Persons with newly diagnosed HIV infection who receive care in the STD treatment setting should be educated concerning what to expect as they enter medical care for HIV infection (51). In nonemergent situations, the initial evaluation of HIV-positive patients usually includes the following:

• a detailed medical history, including sexual and substance abuse history; vaccination history; previous STDs; and specific HIV-related symptoms or diagnoses;
• a physical examination, including a gynecologic examination for women;
• testing for N. gonorrhoeae and C. trachomatis (and for women, a Pap test and wet mount examination of vaginal secretions);
• complete blood and platelet counts and blood chemistry profile;
• toxoplasma antibody test;
• tests for antibodies to HCV; testing for previous or present HAV or HBV infection is recommended if determined to be cost-effective before considering vaccination (see Hepatitis A and Hepatitis B);
• syphilis serology;
• a CD4 T-lymphocyte analysis and determination of HIV plasma viral load;
• a tuberculin skin test (sometimes referred to as a purified protein derivative);
• a urinalysis; and
• a chest radiograph.

Some specialists recommend type-specific testing for HSV-2 if herpes infection status is unknown. A first dose of hepatitis A and/or hepatitis B vaccination for previously unvaccinated persons for whom vaccine is recommended (see Hepatitis A and Hepatitis B) should be administered at this first visit.

In subsequent visits, when the results of laboratory and skin tests are available, antiretroviral therapy may be offered, if indicated, after initial antiretroviral resistance testing is performed (53) and specific prophylactic medications are administered to reduce the incidence of opportunistic infections (e.g., Pneumocystis jiroveci pneumonia, TE, disseminated MAC infection, and TB) (50). The vaccination series for hepatitis A and/or B should be offered for those in whom vaccination is recommended. Influenza vaccination should be offered annually, and pneumococcal vaccination should be given if it has not been administered in the previous 5 years (50,51).

Providers should be alert to the possibility of new or recurrent STDs and should treat such conditions aggressively. The occurrence of an STD in an HIV-infected person is an indication of high-risk behavior and should prompt referral for counseling. Because many STDs are asymptomatic, routine screening for curable STDs (e.g., syphilis, gonorrhea, and chlamydia) should be performed at least yearly for sexually active persons. Women should be screened for cervical cancer precursor lesions by annual Pap smears. More frequent STD screening might be appropriate depending on individual risk behaviors, the local epidemiology of STDs, and whether incident STDs are detected by screening or by the presence of symptoms.

Newly diagnosed HIV-infected persons should receive or be referred for a thorough psychosocial evaluation, including ascertainment of behavioral factors indicating risk for transmitting HIV. Patients might require referral for specific behavioral intervention (e.g., a substance abuse program), mental health disorders (e.g., depression), or emotional distress. They might require assistance with securing and maintaining employment and housing. Women should be counseled or appropriately referred regarding reproductive choices and contraceptive options. Patients with multiple psychosocial problems might be candidates for comprehensive risk-reduction counseling and services (8).

The following are specific recommendations for HIV counseling and referral:

• Persons who test positive for HIV antibody should be counseled, either on site or through referral, concerning the behavioral, psychosocial, and medical implications of HIV infection.
• Health-care providers should be alert for medical or psychosocial conditions that require immediate attention.
• Providers should assess newly diagnosed persons' need for immediate medical care or support and should link them to services in which health-care personnel are experienced in providing care for HIV-infected persons. Such persons might need medical care or services for substance abuse, mental health disorders, emotional distress, reproductive counseling, risk-reduction counseling, and case management. Providers should follow-up to ensure that patients have received the needed services.
• Patients should be educated regarding what to expect in follow-up medical care.

Several innovative interventions for HIV prevention have been developed for diverse at-risk populations, and these can be locally replicated or adapted (11,12). Involvement of nongovernment organizations and community-based organizations might complement such efforts in the clinical setting.

Management of Sex Partners and Injecting-Drug Partners

Clinicians evaluating HIV-infected persons should collect information to determine whether any partners should be notified concerning possible exposure to HIV (6). When referring to persons who are infected with HIV, the term "partner" includes not only sex partners but also IDUs who share syringes or other injection equipment. The rationale for partner notification is that the early diagnosis and treatment of HIV infection in these partners might reduce morbidity and provides the opportunity to encourage risk-reducing behaviors. Partner notification for HIV infection should be confidential and depends on the voluntary cooperation of the patient. Specific guidance regarding spousal notification may vary by jurisdiction.

Two complementary notification processes, patient referral and provider referral, can be used to identify partners. With patient referral, patients directly inform their partners of their exposure to HIV infection. With provider referral, trained health department personnel locate partners on the basis of the names, descriptions, and addresses provided by the patient. During the notification process, the confidentiality of patients is protected; their names are not revealed to partners who are notified. Many state and local health departments provide these services.

The following are specific recommendations for implementing partner-notification procedures:

• HIV-infected patients should be encouraged to notify their partners and to refer them for counseling and testing. If requested by the patient, health-care providers should assist in this process, either directly or by referral to health department partner-notification programs.
• If patients are unwilling to notify their partners or if they cannot ensure that their partners will seek counseling, physicians or health department personnel should use confidential partner notification procedures.
• Partners who are contacted within 72 hours of a high-risk sexual or injecting-drug exposure to an HIV-infected partner, which involves exposure to genital secretions and/or blood, should be offered PEP with combination antiretroviral therapy to complete a 28-day course (58).

Special Considerations

Pregnancy. All pregnant women in the United States should be tested for HIV infection as early during pregnancy as possible. Testing should occur after the patient is notified that she will be tested for HIV as part of the routine panel of prenatal tests, unless she declines (i.e., opt-out screening) (30--32). For women who decline, providers should continue to strongly encourage testing and address concerns that pose obstacles to testing. Women who decline testing because they have had a previous negative HIV test should be informed of the importance of retesting during each pregnancy. Testing pregnant women is particularly important, not only to maintain the health of the patient, but also because interventions (i.e., antiretroviral and obstetrical) can reduce the risk of perinatal transmission of HIV.

After pregnant women have been identified as being HIV-infected, they should be educated about the risk of perinatal infection. Evidence indicates that, in the absence of antiretroviral and other interventions, 15%--25% of infants born to HIV-infected mothers will become infected with HIV; such evidence also indicates that an additional 12%--14% will become infected during breastfeeding where HIV-infected women breastfeed their infants into the second year of life (59,60).

The risk of perinatal HIV transmission can be reduced substantially to <2% through the use of antiretroviral regimens and obstetrical interventions (i.e., zidovudine or nevirapine and elective cesarean section at 38 weeks of pregnancy) and by avoiding breastfeeding (61). Pregnant women who are HIV infected should be counseled concerning their options (either on-site or by referral), given appropriate antenatal treatment, and advised not to breastfeed their infants (for women living in the United States, where infant formula is readily available and can be safely prepared).

HIV Infection Among Infants and Children. Diagnosis of HIV infection in a pregnant woman indicates the need to consider whether other children of the woman might be infected. Infants and young children with HIV infection differ from adults and adolescents with respect to the diagnosis, clinical presentation, and management of HIV disease. For example, because maternal HIV antibody passes through the placenta, antibody tests for HIV are expected to be positive in the sera of both infected and uninfected infants born to seropositive mothers. A definitive determination of HIV infection for an infant aged <18 months is usually based on HIV nucleic acid testing. Management of infants, children, and adolescents who are known or suspected to be infected with HIV requires referral to physicians familiar with the manifestations and treatment of pediatric HIV infection (50,51,62).

Diseases Characterized by Genital Ulcers

Management of Patients Who Have Genital Ulcers

In the United States, the majority of young, sexually active patients who have genital ulcers have either genital herpes, syphilis, or chancroid. The frequency of each condition differs by geographic area and patient population; however, genital herpes is the most prevalent of these diseases. More than one of these diseases can be present in a patient who has genital ulcers. All three of these diseases has been associated with an increased risk for HIV infection. Not all genital ulcers are caused by sexually transmitted infections.

A diagnosis based only on the patient's medical history and physical examination frequently is inaccurate. Therefore, all patients who have genital ulcers should be evaluated with a serologic test for syphilis and a diagnostic evaluation for genital herpes; in settings where chancroid is prevalent, a test for Haemophilus ducreyi should also be performed. Specific tests for evaluation of genital ulcers include 1) syphilis serology and either darkfield examination or direct immunofluorescence test for T. pallidum; 2) culture or antigen test for HSV; and 3) culture for H. ducreyi.

No FDA-cleared PCR test for these organisms is available in the United States; however, such testing can be performed by clinical laboratories that have developed their own tests and conducted a Clinical Laboratory Improvement Amendment (CLIA) verification study. Type-specific serology for HSV-2 might be helpful in identifying persons with genital herpes (see Genital Herpes, Type-Specific Serologic Tests). Biopsy of genital ulcers might be helpful in identifying the cause of ulcers that are unusual or that do not respond to initial therapy. HIV testing should be performed on all patients who have genital ulcers caused by T. pallidum or H. ducreyi, and should be strongly considered for those who have genital ulcers caused by HSV (see Diagnostic Considerations, sections, Syphilis, Chancroid, and Genital Herpes Simplex Virus).

Health-care providers frequently must treat patients before test results are available because early treatment decreases the possibility of ongoing transmission and because successful treatment of genital herpes depends on prompt initiation of therapy. The clinician should treat for the diagnosis considered most likely, on the basis of clinical presentation and epidemiologic circumstances. In some instances, treatment must be initiated for additional conditions because of diagnostic uncertainty. Even after complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no laboratory-confirmed diagnosis.

Chancroid

In the United States, chancroid usually occurs in discrete outbreaks, although the disease is endemic in some areas. Chancroid is a cofactor for HIV transmission, as are genital herpes and syphilis; high rates of HIV infection among patients who have chancroid occur in the United States and other countries. Approximately 10% of persons who have chancroid that was acquired in the United States are coinfected with T. pallidum or HSV; this percentage is higher in persons who have acquired chancroid outside the United States.

A definitive diagnosis of chancroid requires the identification of H. ducreyi on special culture media that is not widely available from commercial sources; even when these media are used, sensitivity is <80%. No FDA-cleared PCR test for H. ducreyi is available in the United States, but such testing can be performed by clinical laboratories that have developed their own PCR test and conducted a CLIA verification study.

The combination of a painful genital ulcer and tender suppurative inguinal adenopathy suggests the diagnosis of chancroid. A probable diagnosis of chancroid, for both clinical and surveillance purposes, can be made if all of the following criteria are met: 1) the patient has one or more painful genital ulcers; 2) the patient has no evidence of T. pallidum infection by darkfield examination of ulcer exudate or by a serologic test for syphilis performed at least 7 days after onset of ulcers; 3) the clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid; and 4) a test for HSV performed on the ulcer exudate is negative.

Treatment

Successful treatment for chancroid cures the infection, resolves the clinical symptoms, and prevents transmission to others. In advanced cases, scarring can result, despite successful therapy.

Recommended Regimens*
Azithromycin 1 g orally in a single dose
OR
Ceftriaxone 250 mg intramuscularly (IM) in a single dose
OR
Ciprofloxacin 500 mg orally twice a day for 3 days
OR
Erythromycin base 500 mg orally three times a day for 7 days

Other Management Considerations

Male patients who are uncircumcised and patients with HIV infection do not respond as well to treatment as those who are circumcised or HIV negative. Patients should be tested for HIV infection at the time chancroid is diagnosed. Patients should be retested for syphilis and HIV 3 months after the diagnosis of chancroid, if the initial test results were negative.

Follow-Up

Patients should be reexamined 3--7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial. The time required for complete healing depends on the size of the ulcer; large ulcers might require >2 weeks. In addition, healing is slower for some uncircumcised men who have ulcers under the foreskin. Clinical resolution of fluctuant lymphadenopathy is slower than resolution for ulcers and might require needle aspiration or incision and drainage. Although needle aspiration of chancroid buboes is a simple procedure, incision and drainage might be preferred because of a reduced need for repeat drainage procedures.

Management of Sex Partners

Sex partners of patients who have chancroid should be examined and treated, regardless of whether symptoms of the disease are present, if they had sexual contact with the patient during the 10 days preceding the patient's onset of symptoms.

Special Considerations

Pregnancy

The safety and efficacy of azithromycin for pregnant and lactating women have not been established. Ciprofloxacin is contraindicated during pregnancy and lactation. No adverse effects of chancroid on pregnancy outcome have been reported.

HIV Infection

HIV-infected patients who have chancroid should be monitored closely because, as a group, these patients are more likely to experience treatment failure and to have ulcers that heal more slowly. HIV-infected patients might require longer courses of therapy than those recommended for HIV-negative patients, and treatment failures can occur with any regimen. Because evidence is limited concerning the therapeutic efficacy of the recommended ceftriaxone and azithromycin regimens in HIV-infected patients, these regimens should be used for such patients only if follow-up can be ensured. Some specialists prefer the erythromycin 7-day regimen for treating HIV-infected persons.

Genital HSV Infections

Genital herpes is a chronic, life-long viral infection. Two types of HSV have been identified, HSV-1 and HSV-2. The majority of cases of recurrent genital herpes are caused by HSV-2 although HSV-1 might become more common as a cause of first episode genital herpes. At least 50 million persons in the United States have genital HSV infection.

The majority of persons infected with HSV-2 have not been diagnosed with genital herpes. Many such persons have mild or unrecognized infections but shed virus intermittently in the genital tract. The majority of genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs.

Diagnosis of HSV Infection

The clinical diagnosis of genital herpes is both insensitive and nonspecific. The classical painful multiple vesicular or ulcerative lesions are absent in many infected persons. Up to 50% of first-episode cases of genital herpes are caused by HSV-1 (63), but recurrences and subclinical shedding are much less frequent for genital HSV-1 infection than genital HSV-2 infection (64,65). Therefore, whether genital herpes is caused by HSV-1 or HSV-2 influences prognosis and counseling. Therefore, the clinical diagnosis of genital herpes should be confirmed by laboratory testing (66). Both virologic and type-specific serologic tests for HSV should be available in clinical settings that provide care for patients with STDs or those at risk for STDs.

Virologic Tests

Isolation of HSV in cell culture is the preferred virologic test for patients who seek medical treatment for genital ulcers or other mucocutaneous lesions. However, the sensitivity of culture is low, especially for recurrent lesions, and declines rapidly as lesions begin to heal. PCR assays for HSV DNA are more sensitive and have been used instead of viral culture (67,68); however, PCR tests are not FDA-cleared for testing of genital specimens. PCR is the test of choice for detecting HSV in spinal fluid for diagnosis of HSV infection of the central nervous system (CNS). Viral culture isolates should be typed to determine if HSV-1 or HSV-2 is the cause of the infection. Lack of HSV detection (i.e., culture or PCR) does not indicate a lack of HSV infection, as viral shedding is intermittent. The use of cytologic detection of cellular changes of HSV infection is an insensitive and nonspecific method of diagnosis, both for genital lesions (i.e., Tzanck preparation) and for cervical Pap smears and should not be relied upon.

Type-Specific Serologic Tests

Both type-specific and nontype-specific antibodies to HSV develop during the first several weeks after infection and persist indefinitely. Accurate type-specific HSV serologic assays are based on the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Such assays first became commercially available in 1999, but older assays that do not accurately distinguish HSV-1 from HSV-2 antibody (despite claims to the contrary) remain on the market. Therefore, the serologic type-specific glycoprotein G (gG)-based assays should be specifically requested when serology is performed (69--71).

The FDA-cleared glycoprotein G-based type-specific assays include the laboratory-based assays HerpeSelect™-1 enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG) or HerpeSelect™-2 ELISA IgG and HerpeSelect™ 1 and 2 Immunoblot IgG (Focus Technology, Inc., Herndon, Virginia), and HSV-2 ELISA (Trinity Biotech USA, Berkeley Heights, New Jersey). Two other assays, Biokit HSV-2 and SureVue HSV-2 (Biokit USA, Lexington, Massachusetts, and Fisher Scientific, Pittsburgh, Pennsylvania, respectively), are point-of-care tests that provide results for HSV-2 antibodies from capillary blood or serum during a clinic visit. The sensitivities of these glycoprotein G type-specific tests for the detection of HSV-2 antibody vary from 80%--98%, and false-negative results might be more frequent at early stages of infection. The specificities of these assays are >96%. False-positive results can occur, especially in patients with a low likelihood of HSV infection. Repeat or confirmatory testing might be indicated in some settings, especially if recent acquisition of genital herpes is suspected.

Because nearly all HSV-2 infections are sexually acquired, the presence of type-specific HSV-2 antibody implies anogenital infection and education and counseling appropriate for persons with genital herpes should be provided. The presence of HSV-1 antibody alone is more difficult to interpret. The majority of persons with HSV-1 antibody have oral HSV infection acquired during childhood, which might be asymptomatic. However, acquisition of genital HSV-1 appears to be increasing, and genital HSV-1 also might be asymptomatic. Lack of symptoms in an HSV-1 seropositive person does not distinguish anogenital from orolabial or cutaneous infection. Persons with HSV-1 infection, regardless of site of infection, remain at risk for HSV-2 acquisition.

Type-specific HSV serologic assays might be useful in the following scenarios: 1) recurrent genital symptoms or atypical symptoms with negative HSV cultures; 2) a clinical diagnosis of genital herpes without laboratory confirmation; and 3) a partner with genital herpes. Some specialists believe that HSV serologic testing should be included in a comprehensive evaluation for STDs among persons with multiple sex partners, HIV infection, and among MSM at increased risk for HIV acquisition. Screening for HSV-1 or HSV-2 in the general population is not indicated.

Principles of Management of Genital Herpes

Antiviral chemotherapy offers clinical benefits to the majority of symptomatic patients and is the mainstay of management. Counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management.

Systemic antiviral drugs can partially control the signs and symptoms of herpes episodes when used to treat first clinical and recurrent episodes, or when used as daily suppressive therapy. However, these drugs neither eradicate latent virus nor affect the risk, frequency, or severity of recurrences after the drug is discontinued. Randomized trials have indicated that three antiviral medications provide clinical benefit for genital herpes: acyclovir, valacyclovir, and famciclovir (72--80). Valacyclovir is the valine ester of acyclovir and has enhanced absorption after oral administration. Famciclovir also has high oral bioavailability. Topical therapy with antiviral drugs offers minimal clinical benefit, and its use is discouraged.

First Clinical Episode of Genital Herpes

Many persons with first-episode herpes have mild clinical manifestations but later develop severe or prolonged symptoms. Therefore, patients with initial genital herpes should receive antiviral therapy.

Recommended Regimens*
Acyclovir 400 mg orally three times a day for 7--10 days
OR
Acyclovir 200 mg orally five times a day for 7--10 days
OR
Famciclovir 250 mg orally three times a day for 7--10 days
OR
Valacyclovir 1 g orally twice a day for 7--10 days

Established HSV-2 infection

The majority of patients with symptomatic, first-episode genital HSV-2 infection subsequently experience recurrent episodes of genital lesions; recurrences are less frequent after initial genital HSV-1 infection. Intermittent asymptomatic shedding occurs in persons with genital HSV-2 infection, even in those with longstanding or clinically silent infection. Antiviral therapy for recurrent genital herpes can be administered either episodically to ameliorate or shorten the duration of lesions or continuously as suppressive therapy to reduce the frequency of recurrences. Many persons, including those with mild or infrequent recurrent outbreaks, benefit from antiviral therapy; therefore, options for treatment should be discussed. Some persons might prefer suppressive therapy, which has the additional advantage of decreasing the risk of genital HSV-2 transmission to susceptible partners (81).

Suppressive Therapy for Recurrent Genital Herpes

Suppressive therapy reduces the frequency of genital herpes recurrences by 70%--80% in patients who have frequent recurrences (i.e., >6 recurrences per year), and many patients report no symptomatic outbreaks. Treatment also is effective in patients with less frequent recurrences. Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as 6 years and with valacyclovir or famciclovir for 1 year. Quality of life frequently is improved in patients with frequent recurrences who receive suppressive therapy, compared with episodic treatment.

The frequency of recurrent genital herpes outbreaks diminishes over time in many patients, and the patient's psychological adjustment to the disease might change. Therefore, periodically during suppressive treatment (e.g., once a year), providers should discuss the need to continue therapy with the patient.

Daily treatment with valacyclovir 500 mg daily decreases the rate of HSV-2 transmission in discordant, heterosexual couples in which the source partner has a history of genital HSV-2 infection (82). Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy to prevent transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences. Suppressive antiviral therapy probably reduces transmission when used by persons who have multiple partners (including MSM) and by those who are HSV-2 seropositive without a history of genital herpes.

Recommended Regimens
Acyclovir 400 mg orally twice a day
OR
Famiciclovir 250 mg orally twice a day
OR
Valacyclovir 500 mg orally once a day
OR
Valacyclovir 1.0 g orally once a day

Valacyclovir 500 mg once a day might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (i.e., >10 episodes per year). Several studies have compared valacyclovir or famciclovir with acyclovir. The results of these studies suggest that valacyclovir and famciclovir are comparable to acyclovir in clinical outcome (74,78,79,83). Ease of administration and cost also are important considerations for prolonged treatment.

Episodic Therapy for Recurrent Genital Herpes

Effective episodic treatment of recurrent herpes requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks. The patient should be provided with a supply of drug or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin.

Recommended Regimens
Acyclovir 400 mg orally three times a day for 5 days
OR
Acyclovir 800 mg orally twice a day for 5 days
OR
Acyclovir 800 mg orally three times a day for 2 days
OR
Famciclovir 125 mg orally twice daily for 5 days
OR
Famciclovir 1000 mg orally twice daily for 1 day
OR
Valacyclovir 500 mg orally twice a day for 3 days
OR
Valacyclovir 1.0 g orally once a day for 5 days

Severe Disease

Intravenous (IV) acyclovir therapy should be provided for patients who have severe HSV disease or complications that necessitate hospitalization (e.g., disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningitis or encephalitis). The recommended regimen is acyclovir 5--10 mg/kg body weight IV every 8 hours for 2--7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy.

Counseling

Counseling of infected persons and their sex partners is critical to the management of genital herpes. The goal of counseling is to 1) help patients cope with the infection and 2) prevent sexual and perinatal transmission (8). Although initial counseling can be provided at the first visit, many patients benefit from learning about the chronic aspects of the disease after the acute illness subsides. Multiple resources, including websites (http://www.ashastd.org and http://www.ihmf.org) and printed materials are available to assist patients, their partners, and clinicians in counseling.

HSV-infected persons might express anxiety concerning genital herpes that does not reflect the actual clinical severity of their disease; the psychological effect of HSV infection frequently is substantial. Common concerns regarding genital herpes include the severity of initial clinical manifestations, recurrent episodes, sexual relationships and transmission to sex partners, and ability to bear healthy children. The misconception that HSV causes cancer should be dispelled. The psychological effect of a serologic diagnosis of HSV-2 infection in a person with asymptomatic or unrecognized genital herpes appears small and transient (84).

The following recommendations apply to counseling of persons with HSV infection:

• Persons who have genital herpes should be educated concerning the natural history of the disease, with emphasis on the potential for recurrent episodes, asymptomatic viral shedding, and the attendant risks of sexual transmission.
• Persons experiencing a first episode of genital herpes should be advised that suppressive therapy is available and is effective in preventing symptomatic recurrent episodes and that episodic therapy sometimes is useful in shortening the duration of recurrent episodes.
• All persons with genital HSV infection should be encouraged to inform their current sex partners that they have genital herpes and to inform future partners before initiating a sexual relationship.
• Sexual transmission of HSV can occur during asymptomatic periods. Asymptomatic viral shedding is more frequent in genital HSV-2 infection than genital HSV-1 infection and is most frequent during the first 12 months after acquiring HSV-2.
• All persons with genital herpes should remain abstinent from sexual activity with uninfected partners when lesions or prodromal symptoms are present.
• The risk of HSV-2 sexual transmission can be decreased by the daily use of valacyclovir by the infected person.
• Recent studies indicate that latex condoms, when used consistently and correctly, might reduce the risk for genital herpes transmission (15,16).
• Sex partners of infected persons should be advised that they might be infected even if they have no symptoms. Type-specific serologic testing of asymptomatic partners of persons with genital herpes is recommended to determine whether risk for HSV acquisition exists.
• The risk for neonatal HSV infection should be explained to all persons, including men. Pregnant women and women of childbearing age who have genital herpes should inform their providers who care for them during pregnancy and those who will care for their newborn infant. Pregnant women who are not infected with HSV-2 should be advised to avoid intercourse during the third trimester with men who have genital herpes. Similarly, pregnant women who are not infected with HSV-1 should be counseled to avoid genital exposure to HSV-1 during the third trimester (e.g., oral sex with a partner with oral herpes and vaginal intercourse with a partner with genital HSV-1 infection).
• Asymptomatic persons diagnosed with HSV-2 infection by type-specific serologic testing should receive the same counseling messages as persons with symptomatic infection. In addition, such persons should be taught about the clinical manifestations of genital herpes.

Management of Sex Partners

The sex partners of patients who have genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions. Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions and offered type-specific serologic testing for HSV infection.

Special Considerations

Allergy, Intolerance, and Adverse Reactions

Allergic and other adverse reactions to acyclovir, valacyclovir, and famciclovir are rare. Desensitization to acyclovir has been described (85).

HIV Infection

Immunocompromised patients might have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and might be severe, painful, and atypical. HSV shedding is increased in HIV-infected persons. Whereas antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs (86). Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons (87--89). HIV-infected persons are likely to be more contagious for HSV; the extent to which suppressive antiviral therapy will decrease HSV transmission from this population is unknown. Some specialists suggest that HSV type-specific serologies be offered to HIV-positive persons during their initial evaluation, and that suppressive antiviral therapy be considered in those who have HSV-2 infection.

Recommended Regimens for Daily Suppressive Therapy in Persons Infected with HIV
Acyclovir 400--800 mg orally twice to three times a day
OR
Famciclovir 500 mg orally twice a day
OR
Valacyclovir 500 mg orally twice a day

Recommended Regimens for Episodic Infection in Persons Infected with HIV
Acyclovir 400 mg orally three times a day for 5--10 days
OR
Famiciclovir 500 mg orally twice a day for 5--10 days
OR
Valacyclovir 1.0 grams orally twice a day for 5--10 days

Acyclovir, valacyclovir, and famciclovir are safe for use in immunocompromised patients in the doses recommended for treatment of genital herpes. For severe HSV disease, initiating therapy with acyclovir 5--10 mg/kg body weight IV every 8 hours might be necessary.

If lesions persist or recur in a patient receiving antiviral treatment, HSV resistance should be suspected and a viral isolate should be obtained for sensitivity testing (90). Such patients should be managed in consultation with an HIV specialist, and alternate therapy should be administered. All acyclovir-resistant strains are resistant to valacyclovir, and the majority are resistant to famciclovir. Foscarnet, 40 mg/kg body weight IV every 8 hours until clinical resolution is attained, is frequently effective for treatment of acyclovir-resistant genital herpes. Topical cidofovir gel 1% applied to the lesions once daily for 5 consecutive days also might be effective. This preparation is not commercially available and must be compounded at a pharmacy.

Genital Herpes in Pregnancy

The majority of mothers of infants who acquire neonatal herpes lack histories of clinically evident genital herpes. The risk for transmission to the neonate from an infected mother is high (30%--50%) among women who acquire genital herpes near the time of delivery and is low (<1%) among women with histories of recurrent herpes at term or who acquire genital HSV during the first half of pregnancy. However, because recurrent genital herpes is much more common than initial HSV infection during pregnancy, the proportion of neonatal HSV infections acquired from mothers with recurrent herpes is substantial. Prevention of neonatal herpes depends both on preventing acquisition of genital HSV infection during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery.

Women without known genital herpes should be counseled to avoid intercourse during the third trimester with partners known or suspected of having genital herpes. In addition, pregnant women without known orolabial herpes should be advised to avoid receptive oral sex during the third trimester with partners known or suspected to have orolabial herpes. Some specialists believe that type-specific serologic tests are useful to identify pregnant women at risk for HSV infection and to guide counseling regarding the risk for acquiring genital herpes during pregnancy. Such testing should be offered to women without genital herpes whose sex partner has HSV infection. The effectiveness of antiviral therapy to decrease the risk for HSV transmission to pregnant women has not been studied.

All pregnant women should be asked whether they have a history of genital herpes. At the onset of labor, all women should be questioned carefully about symptoms of genital herpes, including prodromal symptoms, and all women should be examined carefully for herpetic lesions. Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally. The majority of specialists recommend that women with recurrent genital herpetic lesions at the onset of labor deliver by cesarean section to prevent neonatal herpes. However, cesarean section does not completely eliminate the risk for HSV transmission to the infant.

The safety of systemic acyclovir, valacyclovir, and famciclovir therapy in pregnant women has not been definitively established. Available data do not indicate an increased risk for major birth defects compared with the general population in women treated with acyclovir during the first trimester (91). These findings provide some assurance to women who have had prenatal exposure to acyclovir. The experience with prenatal exposure to valacyclovir and famciclovir is too limited to provide useful information on pregnancy outcomes. Acyclovir may be administered orally to pregnant women with first episode genital herpes or severe recurrent herpes and should be administered IV to pregnant women with severe HSV infection. Acyclovir treatment late in pregnancy reduces the frequency of cesarean sections among women who have recurrent genital herpes by diminishing the frequency of recurrences at term, and many specialists recommend such treatment (92--94). No data support the use of antiviral therapy among HSV seropositive women without a history of genital herpes. The risk for herpes is high in infants of women who acquire genital HSV during late pregnancy; such women should be managed in consultation with an infectious diseases specialist. Some specialists recommend acyclovir therapy in this circumstance, some recommend routine cesarean section to reduce the risk for neonatal herpes, and others recommend both.

Neonatal Herpes

Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a specialist. Some specialists recommend that such infants undergo surveillance cultures of mucosal surfaces to detect HSV infection before development of clinical signs of neonatal herpes. In addition, some specialists recommend the use of acyclovir for infants born to women who acquired HSV near term because the risk for neonatal herpes is high for these infants. All infants who have neonatal herpes should be promptly evaluated and treated with systemic acyclovir. The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the skin and mucous membranes.

Granuloma Inguinale (Donovanosis)

Granuloma inguinale is a genital ulcerative disease caused by the intracellular gram-negative bacterium Klebsiella granulomatis (formerly known as Calymmatobacterium granulomatis). The disease occurs rarely in the United States, although it is endemic in some tropical and developing areas, including India; Papua, New Guinea; central Australia; and southern Africa. Clinically, the disease is commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular (i.e., beefy red appearance) and bleed easily on contact. However, the clinical presentation also can include hypertrophic, necrotic, or sclerotic variants. The causative organism is difficult to culture, and diagnosis requires visualization of dark-staining Donovan bodies on tissue crush preparation or biopsy. No FDA-cleared PCR tests for the detection of K. granulomatis DNA exist, but such an assay might be useful if a CLIA verification study has been conducted. The lesions might develop secondary bacterial infection or can coexist with other sexually transmitted pathogens.

Treatment

A limited number of studies on Donovanosis treatment have been published. Treatment halts progression of lesions, although prolonged therapy is usually required to permit granulation and reepithelialization of the ulcers. Healing typically proceeds inward from the ulcer margins. Relapse can occur 6--18 months after apparently effective therapy. Several antimicrobial regimens have been effective, but a limited number of controlled trials have been published (95).

Recommended Regimen
Doxycycline 100 mg orally twice a day for at least 3 weeks and until all lesions have completely healed

Alternative Regimens
Azithromycin 1 g orally once per week for at least 3 weeks and until all lesions have completely healed
OR
Ciprofloxacin 750 mg orally twice a day for at least 3 weeks and until all lesions have completely healed
OR
Erythromycin base 500 mg orally four times a day for at least 3 weeks and until all lesions have completely healed
OR
Trimethoprim-sulfamethoxazole one double-strength (160 mg/800 mg) tablet orally twice a day for at least 3 weeks and until all lesions have completely healed

Therapy should be continued at least 3 weeks and until all lesions have completely healed. Some specialists recommend the addition of an aminoglycoside (e.g., gentamicin 1 mg/kg IV every 8 hours) to these regimens if improvement is not evident within the first few days of therapy.

Follow-Up

Patients should be followed clinically until signs and symptoms have resolved.

Management of Sex Partners

Persons who have had sexual contact with a patient who has granuloma inguinale within the 60 days before onset of the patient's symptoms should be examined and offered therapy. However, the value of empiric therapy in the absence of clinical signs and symptoms has not been established.

Special Considerations

Pregnancy

Pregnancy is a relative contraindication to the use of sulfonamides. Pregnant and lactating women should be treated with the erythromycin regimen, and consideration should be given to the addition of a parenteral aminoglycoside (e.g., gentamicin). Azithromycin might prove useful for treating granuloma inguinale during pregnancy, but published data are lacking. Doxycycline and ciprofloxacin are contraindicated in pregnant women.

HIV Infection

Persons with both granuloma inguinale and HIV infection should receive the same regimens as those who are HIV negative. Consideration should be given to the addition of a parenteral aminoglycoside (e.g., gentamicin).

Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV) is caused by C. trachomatis serovars L1, L2, or L3 (96). The most common clinical manifestation of LGV among heterosexuals is tender inguinal and/or femoral lymphadenopathy that is typically unilateral. A self-limited genital ulcer or papule sometimes occurs at the site of inoculation. However, by the time patients seek care, the lesions might have disappeared. Rectal exposure in women or MSM might result in proctocolitis (including mucoid and/or hemorrhagic rectal discharge, anal pain, constipation, fever, and/or tenesmus). LGV is an invasive, systemic infection, and if it is not treated early, LGV proctocolitis might lead to chronic, colorectal fistulas and strictures. Genital and colorectal LGV lesions might also develop secondary bacterial infection or might be coinfected with other sexually and nonsexually transmitted pathogens.

Diagnosis is based on clinical suspicion, epidemiologic information, and the exclusion of other etiologies (of proctocolitis, inguinal lymphadenopathy, or genital or rectal ulcers), along with C. trachomatis testing, if available.

Genital and lymph node specimens (i.e., lesion swab or bubo aspirate) may be tested for C. trachomatis by culture, direct immunofluorescence, or nucleic acid detection. Nucleic acid amplification tests (NAAT) for C. trachomatis are not FDA-cleared for testing rectal specimens. Additional procedures (e.g., genotyping) are required for differentiating LGV from non-LGV C. trachomatis but are not widely available.

Chlamydia serology (complement fixation titers >1:64) can support the diagnosis in the appropriate clinical context. Comparative data between types of serologic tests are lacking, and the diagnostic utility of serologic methods other than complement fixation and some microimmunofluorescence procedures has not been established. Serologic test interpretation for LGV is not standardized, tests have not been validated for clinical proctitis presentations, and C. trachomatis serovar-specific serologic tests are not widely available.

In the absence of specific LGV diagnostic testing, patients with a clinical syndrome consistent with LGV, including proctocolitis or genital ulcer disease with lymphadenopathy, should be treated for LGV as described in this report.

Treatment

Treatment cures infection and prevents ongoing tissue damage, although tissue reaction to the injection can result in scarring. Buboes might require aspiration through intact skin or incision and drainage to prevent the formation of inguinal/femoral ulcerations. Doxycycline is the preferred treatment.

Recommended Regimen
Doxycycline 100 mg orally twice a day for 21 days

Alternative Regimen
Erythromycin base 500 mg orally four times a day for 21 days

Some STD specialists believe that azithromycin 1.0 g orally once weekly for 3 weeks is probably effective, although clinical data are lacking.

Follow-Up

Patients should be followed clinically until signs and symptoms have resolved.

Management of Sex Partners

Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient's symptoms should be examined, tested for urethral or cervical chlamydial infection, and treated with a standard chlamydia regimen (azithromycin 1 gm orally x 1 or doxycycline 100 mg orally twice a day for 7 days). The optimum contact interval is unknown; some specialists use longer contact intervals.

Special Considerations

Pregnancy

Pregnant and lactating women should be treated with erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.

HIV Infection

Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.

Syphilis

General Principles

Background

Syphilis is a systemic disease caused by T. pallidum. Patients who have syphilis might seek treatment for signs or symptoms of primary infection (i.e., ulcer or chancre at the infection site), secondary infection (i.e., manifestations that include, but are not limited to, skin rash, mucocutaneous lesions, and lymphadenopathy), or tertiary infection (e.g., cardiac or ophthalmic manifestations, auditory abnormalities, or gummatous lesions). Latent infections (i.e., those lacking clinical manifestations) are detected by serologic testing. Latent syphilis acquired within the preceding year is referred to as early latent syphilis; all other cases of latent syphilis are either late latent syphilis or latent syphilis of unknown duration. Treatment for both late latent syphilis and tertiary syphilis theoretically might require a longer duration of therapy because organisms are dividing more slowly; however, the validity of this concept has not been assessed.

Diagnostic Considerations and Use of Serologic Tests

Darkfield examinations and direct fluorescent antibody (DFA) tests of lesion exudate or tissue are the definitive methods for diagnosing early syphilis. A presumptive diagnosis is possible with the use of two types of serologic tests: 1) nontreponemal tests (e.g., Venereal Disease Research Laboratory [VDRL] and RPR) and 2) treponemal tests (e.g., fluorescent treponemal antibody absorbed [FTA-ABS] and T. pallidum particle agglutination [TP-PA]). The use of only one type of serologic test is insufficient for diagnosis because false-positive nontreponemal test results are sometimes associated with various medical conditions unrelated to syphilis.

Nontreponemal test antibody titers usually correlate with disease activity, and results should be reported quantitatively. A fourfold change in titer, equivalent to a change of two dilutions (e.g., from 1:16--1:4 or from 1:8--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 by using the same testing method (e.g., VDRL or RPR), preferably by 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. Nontreponemal tests usually become nonreactive with time after treatment; however, in some patients, nontreponemal antibodies can persist at a low titer for a long period of time, sometimes for the life of the patient. This response is referred to as the serofast reaction.

The majority of patients who have reactive treponemal tests will have reactive tests for the remainder of their lives, regardless of treatment or disease activity. However, 15%--25% of patients treated during the primary stage revert to being serologically nonreactive after 2--3 years (97). Treponemal test antibody titers do not correlate with disease activity and should not be used to assess treatment response.

Some clinical laboratories and blood banks have begun to screen samples using treponemal EIA tests (98). This strategy will identify both persons with previous treatment and persons with untreated or incompletely treated syphilis. False-positive results can occur, particularly among populations with a low prevalence of syphilis.

Persons with a positive treponemal screening test should have a standard nontreponemal test with titer to guide patient management decisions. If the nontreponemal test is negative, then a different treponemal test should be performed to confirm the results of the initial test. If a second trepomenal test is positive, treatment decisions should be discussed in consultation with a specialist. Some HIV-infected patients can have atypical serologic test results (i.e., unusually high, unusually low, or fluctuating titers). For such patients, when serologic tests do not correspond with clinical syndromes suggestive of early syphilis, use of other tests (e.g., biopsy and direct microscopy) should be considered. However, for the majority of HIV-infected patients, serologic tests are accurate and reliable for the diagnosis of syphilis and for following the r