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CDC Prevention Guidelines Database (Archive)


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This online archive of the CDC Prevention Guidelines Database is being maintained for historical purposes, and has had no new entries since October 1998. To find more recent guidelines, please visit the following:
  • MMWR at http://www.cdc.gov/mmwr/mmwrsrch.htm
  • CDC Web Search at http://www.cdc.gov/search.do


1998 Guidelines for Treatment of Sexually Transmitted Diseases

MMWR 47(RR-1);1-118

Publication date: 01/23/1998


Table of Contents

Expert Consultants

Summary

INTRODUCTION

CLINICAL PREVENTION GUIDELINES
Prevention Messages
Prevention Methods
HIV Prevention Counseling
Partner Notification
Reporting and Confidentiality

SPECIAL POPULATIONS
Pregnant Women
Adolescents
Children

HIV INFECTION: DETECTION, INITIAL MANAGEMENT, AND REFERRAL
Diagnostic Testing for HIV-1 and HIV-2
Acute Retroviral Syndrome
Counseling for HIV-Infected Patients
Planning for Medical Care and for Continuation of Psychosocial Services
Management of Sex Partners and Injecting-Drug Partners
Special Considerations

DISEASES CHARACTERIZED BY GENITAL ULCERS
Management of Patients Who Have Genital Ulcers
Chancroid
Genital Herpes Simplex Virus (HSV) Infection
Granuloma Inguinale (Donovanosis)
Lymphogranuloma Venereum
Syphilis
General Principles
Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
Syphilis in HIV-Infected Persons
Syphilis During Pregnancy

CONGENITAL SYPHILIS

MANAGEMENT OF PATIENTS WHO HAVE A HISTORY OF PENICILLIN ALLERGY

DISEASES CHARACTERIZED BY URETHRITIS AND CERVICITIS
Management of Male Patients Who Have Urethritis
Management of Patients Who Have Nongonococcal Urethritis
Management of Patients Who Have Mucopurulent Cervicitis (MPC)
Chlamydial Infection
Gonococcal Infection

DISEASES CHARACTERIZED BY VAGINAL DISCHARGE
Management of Patients Who Have Vaginal Infections
Bacterial Vaginosis
Trichomoniasis
Vulvovaginal Candidiasis

PELVIC INFLAMMATORY DISEASE (PID)

EPIDIDYMITIS

HUMAN PAPILLOMAVIRUS INFECTION
Genital Warts
Subclinical Genital HPV Infection (Without Exophytic Warts)

CERVICAL CANCER SCREENING FOR WOMEN WHO ATTEND STD CLINICS OR HAVE A HISTORY OF STDs

VACCINE-PREVENTABLE STDs
Hepatitis A
Hepatitis B

PROCTITIS, PROCTOCOLITIS, AND ENTERITIS

ECTOPARASITIC INFECTIONS
Pediculosis Pubis
Scabies

SEXUAL ASSAULT AND STDs
Adults and Adolescents
Sexual Assault or Abuse of Children

Abbreviations Used in This Publication

References

POINT OF CONTACT FOR THIS DOCUMENT:

Tables
Oral desensitization protocol for patients with a positive skin..


Expert Consultants

Chairman: David Atkins, M.D., M.P.H., Agency for Health Care Policy and Research; Presenters: Michael H. Augenbraun, M.D., State University of New York Health Science Center at Brooklyn, NY; Karl Beutner, M.D., Ph.D., Solano Dermatology, Vallejo, CA; Gail A. Bolan, M.D., San Francisco Department of Public Health and University of California at San Francisco; Willard Cates, Jr., M.D., M.P.H., Family Health International, Research Triangle Park, NC; Anne M. Rompalo, M.D., Johns Hopkins University, Baltimore; Pablo J. Sanchez, M.D., Southwestern Medical Center at Dallas; Bradley Stoner, M.D., Ph.D., Washington University School of Medicine, St. Louis, MO; Anna Wald, M.D., M.P.H., University of Washington, Seattle; Cheryl K. Walker, M.D., University of California at Irvine; George D. Wendel, M.D., Southwestern Medical Center at Dallas; Jonathan M. Zenilman, M.D., Johns Hopkins University, Baltimore.

Moderators: King K. Holmes, M.D., Ph.D., Center for AIDS and STDs, University of Washington, Seattle; Edward W. Hook, III, M.D., University of Alabama at Birmingham School of Medicine; A. Eugene Washington, M.D., M.Sc., University of California at San Francisco.

Rapporteurs: John M. Douglas, Jr., M.D., Denver Department of Public Health and University of Colorado Health Science Center; Margaret R. Hammerschlag, M.D., State University of New York Health Science Center; David H. Martin, M.D., Louisiana State University Medical Center, New Orleans.

Consultants: Adaora A. Adimora, M.D., M.P.H., University of North Carolina at Chapel Hill; Virginia A. Caine, M.D., Marion County Health Department, Indianapolis; Laura T. Gutman, M.D., Duke University, Durham, NC; H. Hunter Handsfield, M.D., Seattle-King County Department of Public Health and University of Washington, Seattle; Robert B. Jones, M.D., Ph.D., Indiana University, Indianapolis; Franklyn N. Judson, M.D., Denver Department of Health; William M. McCormack, M.D., State University of New York Health Science Center at Brooklyn; Daniel M. Musher, M.D., Baylor College of Medicine, Houston; Newton G. Osborne, M.D., M.P.H., Howard University Hospital, Washington, DC; Robert T. Rolfs, Jr., M.D., Utah Department of Health; Lawrence L. Sanders, Jr., M.D., Southwest Hospital and Medical Center, Atlanta; Jane R. Schwebke, M.D., University of Alabama at Birmingham School of Medicine; Jack D. Sobel, M.D., Wayne State University School of Medicine, Detroit; David E. Soper, M.D., Medical University of South Carolina, Charleston; Walter E. Stamm, M.D., University of Washington; Lawrence R. Stanberry, M.D., Ph.D., Children's Hospital, Cincinnati; Felicia H. Stewart, M.D., Kaiser Family Foundation, Menlo Park, CA; Richard L. Sweet, M.D., Magee-Women's Hospital, Pittsburgh.

Other Expert Consultants (did not attend meeting): Susan Blank, M.D., New York City Department of Health; Sharon L. Hillier, Ph.D., University of Pittsburgh; Penelope J. Hitchcock, D.V.M., M.S., National Institutes of Health; Paul N. Zenker, M.D., M.P.H., Franklin Primary Health, Mobile, AL.

Liaison Participants: Dennis J. Barbour, J.D., Association of Reproductive Health Professionals; Joan R. Cates, American Social Health Association; JoAnne Doherty, Health Canada, Ontario; Robert G. Harmon, M.D., M.P.H., United Health Care; Kate L. Heilpern, M.D., American College of Emergency Physicians; John J. Henning, Ph.D., American Medical Association; K. King Holmes, M.D., Ph.D., Infectious Diseases Society of America; John N. Krieger, M.D., American Urological Association; Marshall Kubota, M.D., American Academy of Family Practice; Noni E. MacDonald, M.D., American Academy of Pediatrics; Gary A. Richwald, M.D., M.P.H., National Coalition of STD Directors; Helen J. Sawyer, R.N., Georgia Department of Human Resources; Stanley X. Shapiro, M.D., Regional Laboratory and Infectious Disease Committee, Kaiser Permanente, Panorama City, CA; Donald Sutherland, M.D., Health Canada; Steve K. Tyring, M.D., Ph.D., American Academy of Dermatology; C. Johannes van Dam, M.D., World Health Organization; Fernando Zacarias, M.D., M.P.H., Pan American Health Organization, World Health Organization.

CDC/Division of STD Prevention (DSTDP)/STD Treatment Guidelines 1997 Project Coordinators: Kimberly A. Workowski, M.D.; John S. Moran, M.D.; Co-Chair: Michael E. St. Louis, M.D.; Co-Moderator: Katherine M. Stone, M.D.; Presenters: Consuelo M. Beck-Sague, M.D., National Center for Infectious Diseases (NCID); M. Riduan Joesoef, M.D., Ph.D., M.P.H.; Mary L. Kamb, M.D., M.P.H., Division of HIV/AIDS Prevention (DHAP); Jonathan E. Kaplan, M.D., NCID; H. Trent MacKay, M.D., M.P.H.; Michael M. McNeil, M.D., M.P.H., NCID; Allyn K. Nakashima, M.D., DHAP; George P. Schmid, M.D., M.Sc.; Consultants: Sevgi O. Aral, Ph.D.; Stuart M. Berman, M.D.; Donald F. Dowda; Brian R. Edlin, M.D., DHAP; Helene D. Gayle, M.D., M.P.H., National Center for HIV, STD, and TB Prevention (NCHSTP); Robert S. Janssen, M.D., DHAP; Wanda K. Jones, Dr.P.H., Office of Women's Health; William J. Kassler, M.D., M.P.H.; Nancy C. Lee, M.D., DHAP; Beth Macke, Ph.D.; Frank J. Mahoney, M.D., NCID; Phillip I. Nieberg, M.D., M.P.H., NCHSTP; Herbert B. Peterson, M.D., National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP); Martha F. Rogers, M.D., DHAP; William E. Secor, Ph.D., NCID; Dawn K. Smith, M.D., DHAP; Ronald O. Valdiserri, M.D., M.P.H., NCHSTP; Judith N. Wasserheit, M.D., M.P.H.; Lynne S. Wilcox, M.D., NCCDPHP; Support Staff: Cynthia Ford, Contractor; Deborah McElroy; Garrett K. Mallory.


Summary

These guidelines for the treatment of patients who have sexually transmitted diseases (STDs) were developed by CDC staff members after consultation with a group of invited experts who met in Atlanta on February 10-12, 1997. The information in this report updates the "1993 Sexually Transmitted Diseases Treatment Guidelines" (MMWR 1993;42{no. RR-14}). Included are new recommendations for treatment of primary and recurrent genital herpes and management of pelvic inflammatory disease; a new patient-applied medication for treatment of genital warts; and a revised approach to the management of victims of sexual assault. Revised sections describe the evaluation of urethritis and the diagnostic evaluation of congenital syphilis. These guidelines also include expanded sections concerning STDs among infants, children, and pregnant women and the management of patients who have asymptomatic human immunodeficiency virus infection, genital warts, and genital herpes. Guidelines are provided for vaccine-preventable STDs, including recommendations for the use of hepatitis A and hepatitis B vaccines.


INTRODUCTION

Physicians and other health-care providers have a critical role in preventing and treating sexually transmitted diseases (STDs). These recommendations for the treatment of STDs, which were developed by CDC staff members in consultation with a group of invited experts, are intended to assist with that effort.

This report was produced through a multi-stage process. Beginning in the spring of 1996, CDC personnel and invited experts systematically reviewed literature concerning each of the major STDs, focusing on information that had become available since the "1993 Sexually Transmitted Diseases Treatment Guidelines" (MMWR 1993;42{no. RR-14}) were published. Background papers were written and tables of evidence 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. For these reviews, published abstracts and peer-reviewed journal articles were considered. A draft document was developed on the basis of the reviews.

In February 1997, invited consultants assembled in Atlanta for a 3-day meeting. CDC personnel and invited experts presented the key questions on STD treatment suggested from the literature reviews and presented the information available to answer those questions. Where relevant, the questions focused on four principal outcomes of STD therapy: a) microbiologic cure, b) alleviation of signs and symptoms, c) prevention of sequelae, and d) prevention of transmission. Cost-effectiveness and other advantages (e.g., single-dose formulations and directly observed therapy) of specific regimens also were considered. The consultants then assessed whether the questions identified were appropriate, 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 described previously. The sections concerning adolescents, congenital syphilis, and partner notification were reviewed by other CDC experts on prevention of STDs and human immunodeficiency virus (HIV) infection. The recommendations for STD screening during pregnancy were developed after CDC staff reviewed the published recommendations of other expert groups. The sections concerning early HIV infection are a compilation of recommendations developed by CDC experts in HIV infection. The sections on hepatitis B virus (HBV) (1) and hepatitis A virus (HAV) (2) infections are based on previously published recommendations of the Advisory Committee on Immunization Practices (ACIP).

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 1998. When more than one therapeutic regimen is recommended, the sequence is alphabetized unless there is priority of choice (i.e., based on efficacy, convenience, and cost). Almost all recommended regimens have similar efficacy and similar rates of intolerance or toxicity unless otherwise specified.

These recommendations were developed in consultation with experts whose experience is primarily with the treatment of patients in public STD clinics. Nevertheless, these recommendations also should be applicable to other patient-care settings, including family planning clinics, private physicians' offices, managed care organizations, and other primary-care facilities. When using these guidelines, the disease prevalence and other characteristics of the medical practice setting should be considered. These recommendations should be regarded as a source of clinical guidance and not as standards or inflexible rules.

These recommendations focus on the treatment and counseling of individual patients and do not address other community services and interventions that are important in STD/HIV prevention. Clinical and laboratory diagnoses are described when such information is related to therapy. For a more comprehensive discussion of diagnosis, refer to CDC's Sexually Transmitted Diseases Clinical Practice Guidelines, 1991 (3).


CLINICAL PREVENTION GUIDELINES

The prevention and control of STDs is based on five major concepts: first, education of those at risk on ways to reduce the risk for STDs; second, detection of asymptomatically infected persons and of symptomatic persons unlikely to seek diagnostic and treatment services; third, effective diagnosis and treatment of infected persons; fourth, evaluation, treatment, and counseling of sex partners of persons who are infected with an STD; and fifth, preexposure vaccination of persons at risk for vaccine-preventable STDs. Although this report focuses primarily on the clinical aspects of STD control, prevention of STDs is based on changing the sexual behaviors that place persons at risk for infection. Moreover, because STD control activities reduce the likelihood of transmission to sex partners, prevention for individuals constitutes prevention for the community.

Clinicians have the opportunity to provide client education and counseling and to participate in identifying and treating infected sex partners in addition to interrupting transmission by treating persons who have the curable bacterial and parasitic STDs. The ability of the health-care provider to obtain an accurate sexual history is crucial in prevention and control efforts. Guidance in obtaining a sexual history is available in the chapter "Sexuality and Reproductive Health" in Contraceptive Technology, 16th edition (4). The accurate diagnosis and timely reporting of STDs by the clinician is the basis for effective public health surveillance.

Prevention Messages

Preventing the spread of STDs requires that persons at risk for transmitting or acquiring infections change their behaviors. The essential first step is for the health-care provider to proactively include questions regarding the patient's sexual history as part of the clinical interview. When risk factors have been identified, the provider has an opportunity to deliver prevention messages. Counseling skills (i.e., respect, compassion, and a nonjudgmental attitude) are essential to the effective delivery of prevention messages. Techniques that can be effective in facilitating a rapport with the patient include using open-ended questions, using understandable language, and reassuring the patient that treatment will be provided regardless of considerations such as ability to pay, citizenship or immigration status, language spoken, or lifestyle.

Prevention messages should be tailored to the patient, with consideration given to the patient's specific risk factors for STDs. Messages should include a description of specific actions that the patient can take to avoid acquiring or transmitting STDs (e.g., abstinence from sexual activity if STD-related symptoms develop).

Sexual Transmission

The most effective way to prevent sexual transmission of HIV infection and other STDs is to avoid sexual intercourse with an infected partner. Counseling that provides information concerning abstinence from penetrative sexual intercourse is crucial for a) persons who are being treated for an STD or whose partners are undergoing treatment and b) persons who wish to avoid the possible consequences of sexual intercourse (e.g., STD/HIV and pregnancy). A more comprehensive discussion of abstinence is available in Contraceptive Technology, 16th edition (4).

Injecting-Drug Users

The following prevention messages are appropriate for injecting-drug users:

Preexposure Vaccination

Preexposure vaccination is one of the most effective methods used to prevent transmission of certain STDs. HBV infection frequently is sexually transmitted, and hepatitis B vaccination is recommended for all unvaccinated patients being evaluated for an STD. In the United States, hepatitis A vaccines from two manufacturers were licensed recently. Hepatitis A vaccination is recommended for several groups of patients who might seek treatment in STD clinics; such patients include homosexual or bisexual men and persons who use illegal drugs. Vaccine trials for other STDs are being conducted, and vaccines for these STDs may become available within the next several years.

Prevention Methods

Male Condoms

When used consistently and correctly, condoms are effective in preventing many STDs, including HIV infection. Multiple cohort studies, including those of serodiscordant sex partners, have demonstrated a strong protective effect of condom use against HIV infection. Because condoms do not cover all exposed areas, they may be more effective in preventing infections transmitted between mucosal surfaces than those transmitted by skin-to-skin contact. 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 low in the United States (i.e., usually two broken condoms per 100 condoms used). Condom failure usually results from inconsistent or incorrect use rather than condom breakage.

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

Female Condoms

Laboratory studies indicate that the female condom (Reality (TM)) -- 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. Other than one investigation of recurrent trichomoniasis, no clinical studies have been completed to evaluate the efficacy of female condoms in providing protection from STDs, including HIV. If used consistently and correctly, the female condom should substantially reduce the risk for STDs. When a male condom cannot be used appropriately, sex partners should consider using a female condom.

Condoms and Spermicides

Whether condoms lubricated with spermicides are more effective than other lubricated condoms in protecting against the transmission of HIV and other STDs has not been determined. Furthermore, spermicide-coated condoms have been associated with Escherichia coli urinary tract infection in young women. Whether condoms used with vaginal application of spermicide are more effective than condoms used without vaginal spermicides also has not been determined. Therefore, the consistent use of condoms, with or without spermicidal lubricant or vaginal application of spermicide, is recommended.

Vaginal Spermicides, Sponges, and Diaphragms

As demonstrated in several randomized controlled trials, vaginal spermicides used alone without condoms reduce the risk for cervical gonorrhea and chlamydia. However, vaginal spermicides offer no protection against HIV infection, and spermicides are not recommended for HIV prevention. The vaginal contraceptive sponge, which is not available in the United States, protects against cervical gonorrhea and chlamydia, but its use increases the risk for candidiasis. In case-control and cross-sectional studies, diaphragm use has been demonstrated to protect against cervical gonorrhea, chlamydia, and trichomoniasis; however, no cohort studies have been conducted. Vaginal sponges or diaphragms should not be assumed to protect women against HIV infection. The role of spermicides, sponges, and diaphragms for preventing STDs in men has not been evaluated.

Nonbarrier Contraception, Surgical Sterilization, and Hysterectomy

Women who are not at risk for pregnancy might incorrectly perceive themselves to be at no risk for STDs, including HIV infection. Nonbarrier contraceptive methods offer no protection against HIV or other STDs. Hormonal contraception (e.g., oral contraceptives, Norplant (TM), and Depo-Provera (TM)) has been associated in some cohort studies with cervical STDs and increased acquisition of HIV; however, data concerning this latter finding are inconsistent. Women who use hormonal contraception, have been surgically sterilized, or have had hysterectomies should be counseled regarding the use of condoms and the risk for STDs, including HIV infection.

HIV Prevention Counseling

Knowledge of HIV status and appropriate counseling are important components in initiating behavior change. Therefore, HIV counseling is an important HIV prevention strategy, although its efficacy in reducing risk behaviors is still being evaluated. By ensuring that counseling is empathic and client-centered, clinicians can develop a realistic appraisal of the patient's risk and help the patient develop a specific and realistic HIV prevention plan (5).

Counseling associated with HIV testing has two main components: pretest and posttest counseling. During pretest counseling, the clinician should conduct a personalized risk assessment, explain the meaning of positive and negative test results, ask for informed consent for the HIV test, and help the patient develop a realistic, personalized risk-reduction plan. During posttest counseling, the clinician should inform the patient of the results, review the meaning of the results, and reinforce prevention messages. If the patient has a confirmed positive HIV test result, posttest counseling should include referral for follow-up medical services and, if needed, social and psychological services. HIV-negative patients at continuing risk for HIV infection also may benefit from referral for additional counseling and prevention services.

Partner Notification

For most STDs, partners of patients should be examined. When exposure to a treatable STD is considered likely, appropriate antimicrobials should be administered even though no clinical signs of infection are evident and laboratory test results are not yet available. In many states, the local or state health department can assist in notifying the partners of patients who have selected STDs (e.g., HIV infection, syphilis, gonorrhea, hepatitis B, and chlamydia).

Health-care providers should advise patients who have an STD to notify sex partners, including those without symptoms, of their exposure and encourage these partners to seek clinical evaluation. This type of partner notification is known as patient referral. In situations in which patient referral may not be effective or possible, health departments should be prepared to assist the patient either through contract referral or provider referral. Contract referral is the process by which patients agree to self-refer their partners within a defined time period. If the partners do not obtain medical evaluation and treatment within that period, then provider referral is implemented. Provider referral is the process by which partners named by infected patients are notified and counseled by health department staff.

Interrupting the transmission of infection is crucial to STD control. For treatable and vaccine-preventable STDs, further transmission and reinfection can be prevented by referral of sex partners for diagnosis, treatment, vaccination (if applicable), and counseling. When health-care providers refer infected patients to local or state health departments for provider-referral partner notification, the patients may be interviewed by trained professionals to obtain the names of their sex partners and information regarding the location of these partners for notification purposes. Every health department protects the privacy of patients in partner-notification activities. Because of the advantage of confidentiality, many patients prefer that public health officials notify partners. However, the ability of public health officials to provide appropriate prophylaxis to contacts of all patients who have STDs may be limited. In situations where the number of anonymous partners is substantial (e.g., situations among persons who exchange sex for drugs), targeted screening of persons at risk may be more effective at stopping the transmission of disease than provider-referral partner notification. Guidelines for management of sex partners and recommendations for partner notification for specific STDs are included for each STD addressed in this report.

Reporting and Confidentiality

The accurate identification and timely reporting of STDs are integral components of successful disease control efforts. Timely reporting is important for assessing morbidity trends, targeting limited resources, and assisting local health authorities in identifying sex partners who may be infected. STD/HIV and acquired immunodeficiency syndrome (AIDS) cases should be reported in accordance with local statutory requirements.

Syphilis, gonorrhea, and AIDS are reportable diseases in every state. Chlamydial infection is reportable in most states. The requirements for reporting other STDs differ by state, and clinicians should be familiar with local STD reporting requirements. Reporting may be provider- and/or laboratory-based. Clinicians who are unsure of local reporting requirements should seek advice from local health departments or state STD programs.

STD and HIV reports are maintained in strictest confidence; in most jurisdictions, such reports are protected by statute from subpoena. Before public health representatives conduct follow-up of a positive STD-test result, these persons 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 fatal or severely debilitating effects on a fetus. Pregnant women and their sex partners should be questioned about STDs and should be counseled about the possibility of perinatal infections.

Recommended Screening Tests

Other Concerns

Other STD-related concerns are to be considered as follows:

For a more detailed discussion of these guidelines, as well as for infections not transmitted sexually, refer to Guidelines for Perinatal Care (6).

NOTE: The sources for these guidelines for screening of pregnant women include the Guide to Clinical Preventive Services (7), Guidelines for Perinatal Care (6), American College of Obstetricians and Gynecologists (ACOG) Technical Bulletin: Gonorrhea and Chlamydial Infections (8), "Recommendations for the Prevention and Management of Chlamydia trachomatis Infections" (9), and "Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States through Universal Childhood Vaccination -- Recommendations of the Immunization Practices Advisory Committee (ACIP)" (1). These sources are not entirely compatible in their recommendations. 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 recommend that pregnant women at high risk for chlamydia be screened for the 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 more extensive (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. Physicians should select a screening strategy that is compatible with the population and setting of their medical practices and that meets their goals for STD case detection and treatment.

Adolescents

Health-care providers who provide care for adolescents should be aware of several issues that relate specifically to these persons. The rates of many STDs are highest among adolescents (e.g., the rate of gonorrhea is highest among females aged 15-19 years). Clinic-based studies have demonstrated that the prevalence of chlamydial infections, and possibly of human papillomavirus (HPV) infections, also is highest among adolescents. In addition, surveillance data indicate that 9% of adolescents who have acute HBV infection either a) have had sexual contact with a chronically infected person or with multiple sex partners or b) gave 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 be administered hepatitis B vaccine.

Adolescents who are at high risk for STDs include male homosexuals, sexually active heterosexuals, clients in STD clinics, and injecting-drug users. Younger adolescents (i.e., persons aged less than 15 years) who are sexually active are at particular risk for infection. Adolescents are at greatest risk for STDs because they frequently have unprotected intercourse, are biologically more susceptible to infection, and face multiple obstacles to utilization of health care.

Several of these issues can be addressed by clinicians who provide services to adolescents. Clinicians can address the general lack of knowledge and awareness about the risks and consequences of STDs and offer guidance, constituting true primary prevention, to help adolescents develop healthy sexual behaviors and prevent the establishment of patterns of behavior that can undermine sexual health. With limited exceptions, all adolescents in the United States can consent to the confidential diagnosis and treatment of STDs. Medical care for STDs can be provided to adolescents without parental consent or knowledge. Furthermore, in many 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. Providers should appreciate how important confidentiality is to adolescents and should strive to follow policies that comply with state laws to ensure the confidentiality of STD-related services provided to adolescents.

The style and content of counseling and health education should be adapted for adolescents. Discussions should be appropriate for the patient's developmental level and should identify risky behaviors, such as sex and drug-use behaviors. Careful counseling and thorough discussions are especially important for adolescents who may not acknowledge engaging in high-risk behaviors. Care and counseling should be direct and nonjudgmental.

Children

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


HIV INFECTION: DETECTION, INITIAL MANAGEMENT, 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 is variable. 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). Most adults and adolescents infected with HIV remain symptom-free for long periods, but viral replication is active during all stages of infection, increasing substantially as the immune system deteriorates. AIDS eventually develops in almost all HIV-infected persons; in one study of HIV-infected adults, AIDS developed in 87% (95% confidence interval {CI}=83%-90%) within 17 years after infection. Additional cases are expected to occur among those who have remained AIDS-free for longer periods.

Greater awareness among both patients and health-care providers of the risk factors associated with HIV transmission has led to increased testing for HIV and earlier diagnosis of the infection, often before symptoms develop. The early diagnosis of HIV infection is important for several reasons. Treatments are available to slow the decline of immune system function. HIV-infected persons who have altered immune function are at increased risk for infections for which preventive measures are available (e.g., Pneumocystis carinii pneumonia {PCP}, toxoplasmic 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 many other diseases and may affect the efficacy of antimicrobial therapy for some STDs. Finally, the early diagnosis of HIV enables the health-care provider to counsel such patients and to assist in preventing HIV transmission to others.

Proper management of HIV infection involves a complex array of behavioral, psychosocial, and medical services. Although some of these services may be available in the STD treatment facility, other services, particularly medical services, are usually unavailable in this setting. Therefore, referral to a health-care provider or facility experienced in caring for HIV-infected patients is advised. Staff in STD treatment facilities should be knowledgeable about the options for referral available in their communities. While in the STD treatment facility, the HIV-infected patient should be educated about HIV infection and the various options for HIV care that are available.

Because of the complexity of services required for management of HIV infection, detailed information, particularly regarding medical care, is beyond the scope of this report and may be found elsewhere (3,5,10,11). Rather, this section provides information on diagnostic testing for HIV-1 and HIV-2, counseling patients who have HIV infection, and preparing the HIV-infected patient for what to expect when medical care is necessary. Information also is provided on management of sex partners, because such services can and should be provided in the STD treatment facility before referral. Finally, the topics of HIV infection during pregnancy and in infants and children are addressed.

Diagnostic Testing for HIV-1 and HIV-2

Testing for HIV should be offered to all persons whose behavior puts them at risk for infection, including persons who seek evaluation and treatment for STDs. Counseling before and after testing (i.e., pretest and posttest counseling) is an integral part of the testing procedure (see HIV Prevention Counseling). Informed consent must be obtained before an HIV test is performed. Some states require written consent.

HIV infection usually is diagnosed by using HIV-1 antibody tests. Antibody testing begins with a sensitive screening test such as the enzyme immunoassay (EIA). Reactive screening tests must be confirmed by a supplemental test, such as the Western blot (WB) or an immunofluorescence assay (IFA). 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 6 months after infection. Although a negative antibody test result usually indicates that a person is not infected, antibody tests cannot exclude infection that occurred less than 6 months before the test.

The prevalence of HIV-2 in the United States is extremely low, and CDC does not recommend routine testing for HIV-2 in settings other than blood centers, unless demographic or behavioral information indicates that HIV-2 infection might be present. Those at risk for HIV-2 infection include persons from a country in which HIV-2 is endemic or the sex partners of such persons. HIV-2 is endemic in parts of West Africa, and an increased prevalence of HIV-2 has been reported in Angola, France, Mozambique, and Portugal. In addition, testing for HIV-2 should be conducted when there is clinical evidence or suspicion of HIV disease in the absence of a positive test for antibodies to HIV-1 (12).

Because HIV antibody crosses the placenta, its presence in a child aged less than 18 months is not diagnostic of HIV infection (see Special Considerations, HIV Infection in Infants and Children).

The following are specific recommendations for diagnostic testing for HIV infection:

Acute Retroviral Syndrome

Health-care providers should be alert for 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 to detect the presence of HIV. Recent data indicate that initiation of antiretroviral therapy during this period can delay the onset of HIV-related complications and might influence prognosis. If testing reveals acute HIV infection, health-care providers should either counsel the patient about immediate initiation of antiretroviral therapy or refer the patient for emergency expert consultation. The optimal antiretroviral regimen at this time is unknown. Treatment with zidovudine can delay the onset of HIV-related complications; however, most experts recommend treatment with two nucleoside reverse transcriptase inhibitors and a protease inhibitor.

Counseling for HIV-Infected Patients

Behavioral and psychosocial services are an integral part of health care for HIV-infected patients; such services should be available on-site or through referral when HIV infection is diagnosed. Patients often are distressed when first informed of a positive HIV test result. Such patients face several major adaptive challenges: a) accepting the possibility of a shortened life span, b) coping with others' reactions to a stigmatizing illness, c) developing and adopting strategies for maintaining physical and emotional health, and d) initiating changes in behavior to prevent HIV transmission to others. Many patients also require assistance with making reproductive choices, gaining access to health services, and confronting employment or housing discrimination.

Interrupting HIV transmission depends on behavioral changes made by those persons at risk for transmitting or acquiring infection. Infected persons, as potential sources of new infections, must receive additional counseling and assistance to support partner notification and counseling to prevent infection of others. Targeting behavior change programs toward HIV-infected persons and their sex partners, or those with whom they share injecting-drug equipment, is an important adjunct to AIDS prevention efforts.

The following are specific recommendations for counseling HIV-infected patients:

Planning for Medical Care and for Continuation of Psychosocial Services

Practice settings for offering HIV care differ depending on local resources and needs. Primary-care providers and outpatient facilities must ensure that appropriate resources are available for each patient and must avoid fragmentation of care as much as possible. A single source that is able to provide comprehensive care for all stages of HIV infection is preferred; however, the limited availability of such resources often results in the need to coordinate care among outpatient, inpatient, and specialist providers in different locations. Providers should do everything possible to avoid fragmentation of care and long delays between diagnosis of HIV infection and access to medical and psychosocial services.

Recently identified HIV infection may not have been recently acquired. Persons newly diagnosed with HIV may be at any of the different stages of infection. Therefore, the health-care provider 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 medical care. Similarly, the provider should be alert for signs of severe psychologic distress and be prepared to refer the client accordingly.

HIV-infected patients in the STD treatment setting should be educated about what to expect when medical care is necessary (11). In the nonemergent situation, the initial evaluation of the HIV-positive patient usually includes the following components:

In subsequent visits, once the results of laboratory and skin tests are available, the patient may be offered antiretroviral therapy (16), as well as specific medications to reduce the incidence of opportunistic infections (e.g., PCP, TE, disseminated MAC infection, and TB) (10,14,17-19). Hepatitis B vaccination should be offered to patients who do not have hepatitis B markers, influenza vaccination should be offered annually, and pneumococcal vaccination should be administered. For additional information concerning vaccination of HIV-infected patients, refer to "Recommendations of the Advisory Committee on Immunization Practices (ACIP): Use of Vaccines and Immune Globulins in Persons with Altered Immunocompetence" (20).

Specific recommendations for planning medical care and continuation of psychosocial services include the following:

Management of Sex Partners and Injecting-Drug Partners

When referring to persons who are infected with HIV, the term "partner" includes not only sex partners but also injecting-drug users who share syringes or other injection equipment. The rationale for partner notification is that the early diagnosis and treatment of HIV infection possibly reduces morbidity and provides the opportunity to encourage risk-reducing behaviors. Partner notification for HIV infection must be confidential and will depend on voluntary cooperation of the patient.

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 anonymity of patients is protected; their names are not revealed to partners who are notified. Many state health departments provide assistance, if requested, with provider-referral partner notification.

The results of one randomized trial suggested that provider referral is more effective in notifying partners than patient referral. In that study, 50% of partners in the provider-referral group were notified, compared with 7% of partners notified by persons in the patient-referral group. However, whether behavioral change takes place as a result of partner notification has not been determined, and many patients are reluctant to disclose the names of partners because of concern about discrimination, disruption of relationships, loss of confidentiality for the partners, and possible violence.

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

Special Considerations

Pregnancy

All pregnant women should be offered HIV testing as early in pregnancy as possible (21). This recommendation is particularly important because of the available treatments for reducing the likelihood of perinatal transmission and maintaining the health of the woman. HIV-infected women should be informed specifically about the risk for perinatal infection. Current evidence indicates that 15%-25% of infants born to untreated HIV-infected mothers are infected with HIV; the virus also can be transmitted from an infected mother by breastfeeding. Zidovudine (ZDV) reduces the risk for HIV transmission to the infant from approximately 25% to 8% if administered to women during the later stage of pregnancy and during labor and to infants for the first 6 weeks of life (22). Therefore, ZDV treatment should be offered to all HIV-infected pregnant women. In the United States, HIV-infected women should be advised not to breastfeed their infants.

Insufficient information is available regarding the safety of ZDV or other antiretroviral drugs during early pregnancy; however, on the basis of the ACTG-076 protocol, *(1) ZDV is indicated for the prevention of maternal-fetal HIV transmission as part of a regimen that includes oral ZDV at 14-34 weeks of gestation, intravenous (IV) ZDV during labor, and ZDV Syrup to the neonate after birth (22). Glaxo Wellcome, Inc., Hoffmann-LaRoche, Inc., Bristol-Myers Squibb, Co., and Merck & Co., Inc., in cooperation with CDC, maintain a registry to assess the safety of ZDV, didanosine (ddI), lamivudine (3TC), saquinavir (SAQ), stavudine (d4t), and dideoxycytodine (ddC) during pregnancy. Women who receive any of these drugs during pregnancy should be reported to this registry; telephone (800) 722-9292, extension 38465. The number of cases reported through February 1997 represented a sample of insufficient size for reliably estimating the risk for birth defects after administration of ddI, 3TC, SAQ, d4t, ddC, or ZDV, or their combination, to pregnant women and their fetuses. However, the registry findings did not indicate an increase in the number of birth defects after receipt of only ZDV in comparison with the number expected in the U.S. population. Furthermore, no consistent pattern of birth defects has been observed that would suggest a common cause.

Women should be counseled about their options regarding pregnancy. The objective of counseling is to provide HIV-infected women with information for making reproductive decisions, analogous to the model used in genetic counseling. In addition, contraceptive counseling should be offered to HIV-infected women who do not desire pregnancy. Prenatal and abortion services should be available on-site or by referral. Pregnancy among HIV-infected women does not appear to increase maternal morbidity or mortality.

HIV Infection in Infants and Children

HIV-infected infants and young children differ from adults and adolescents with respect to the diagnosis, clinical presentation, and management of HIV disease. For example, because of transplacental passage of maternal HIV antibody, both infected and uninfected infants born to HIV-infected mothers are expected to have positive HIV-antibody test results. A definitive determination of HIV infection in a child less than 18 months of age should be based on laboratory evidence of HIV in blood or tissues by culture, nucleic acid, or antigen detection. In addition, CD4+ lymphocyte counts are higher in infants and children aged less than 5 years than in healthy adults and must be interpreted accordingly. All infants born to HIV-infected mothers should begin PCP prophylaxis at age 4-6 weeks; such prophylaxis should be continued until HIV infection has been excluded (18). Other modifications must be made in health services that are recommended for infants and children, such as avoiding vaccination with live oral polio vaccine when a child (or household contact) is infected with HIV. 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.

*(1) The Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Protocol 076, a clinical trial sponsored by the National Institutes of Health in collaboration with the National Institute of Health and Medical Research and the National Agency of Research on AIDS in France.


DISEASES CHARACTERIZED BY GENITAL ULCERS

Management of Patients Who Have Genital Ulcers

In the United States, most young, sexually active patients who have genital ulcers have either genital herpes, syphilis, or chancroid. The relative frequency of each differs by geographic area and patient population; however, in most areas of the United States, genital herpes is the most prevalent of these diseases. More than one of these diseases could be present in a patient who has genital ulcers. Each disease has been associated with an increased risk for HIV infection.

A diagnosis based only on the patient's medical history and physical examination often is inaccurate. Therefore, evaluation of all patients who have genital ulcers should include a serologic test for syphilis and diagnostic evaluation for herpes. Although, ideally, all of these tests should be conducted for each patient who has a genital ulcer, use of such tests (other than a serologic test for syphilis) may be based on test availability and clinical or epidemiologic suspicion. Specific tests for the evaluation of genital ulcers include the following:

Polymerase chain reaction (PCR) tests for these organisms might become available commercially.

HIV testing should be a) performed in the management of patients who have genital ulcers caused by T. pallidum or H. ducreyi and b) considered for those who have ulcers caused by HSV (see sections on Syphilis, Chancroid, and Genital Herpes).

A health-care provider often must treat a patient before test results are available. In such a circumstance, the clinician should treat for the diagnosis considered most likely. If the diagnosis is unclear, many experts recommend treatment for syphilis, or for both syphilis and chancroid if the patient resides in a community in which H. ducreyi is a significant cause of genital ulcers, especially when diagnostic capabilities for chancroid or syphilis are not ideal. However, even after complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no laboratory-confirmed diagnosis.

Chancroid

Chancroid is endemic in some areas of the United States, and the disease also occurs in discrete outbreaks. Chancroid is a cofactor for HIV transmission, and high rates of HIV infection among patients who have chancroid have been reported in the United States and other countries. An estimated 10% of patients who have chancroid could be coinfected with T. pallidum or HSV.

A definitive diagnosis of chancroid requires identification of H. ducreyi on special culture media that are not widely available from commercial sources; even using these media, sensitivity is less than or equal to 80%. A probable diagnosis, for both clinical and surveillance purposes, may be made if the following criteria are met: a) the patient has one or more painful genital ulcers; b) 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; and c) the clinical presentation, appearance of genital ulcers, and regional lymphadenopathy, if present, are typical for chancroid and a test for HSV is negative. The combination of a painful ulcer and tender inguinal adenopathy, which occurs among one third of patients, suggests a diagnosis of chancroid; when accompanied by suppurative inguinal adenopathy, these signs are almost pathognomonic. PCR testing for H. ducreyi might become available soon.

Treatment

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

Recommended Regimen

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 four times a day for 7 days.

NOTE: Ciprofloxacin is contraindicated for pregnant and lactating women and for persons aged less than 18 years.

All four regimens are effective for treatment of chancroid in HIV-infected patients. Azithromycin and ceftriaxone offer the advantage of single-dose therapy. Worldwide, several isolates with intermediate resistance to either ciprofloxacin or erythromycin have been reported.

Other Management Considerations

Patients who are uncircumcised and HIV-infected patients might 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 3 months after the diagnosis of chancroid if the initial test results for syphilis and HIV were negative.

Follow-Up

Patients should be reexamined 3-7 days after initiation of therapy. If treatment is successful, ulcers improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether a) the diagnosis is correct, b) the patient is coinfected with another STD, c) the patient is infected with HIV, d) the treatment was not taken as instructed, or e) 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 may require greater than 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 that of ulcers and may require drainage, even during otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage of buboes may be preferred because of less need for subsequent 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 onset of symptoms in the patient.

Special Considerations

Pregnancy

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

HIV Infection

HIV-infected patients who have chancroid should be monitored closely. Such patients may require longer courses of therapy than those recommended for HIV-negative patients. Healing may be slower among HIV-infected patients, and treatment failures occur with any regimen. Because data are 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 experts suggest using the erythromycin 7-day regimen for treating HIV-infected persons.

Genital Herpes Simplex Virus (HSV) Infection

Genital herpes is a recurrent, incurable viral disease. Two serotypes of HSV have been identified: HSV-1 and HSV-2. Most cases of recurrent genital herpes are caused by HSV-2. On the basis of serologic studies, genital HSV-2 infection has been diagnosed in at least 45 million persons in the United States.

Most HSV-2-infected persons have not received a diagnosis of genital herpes. Such persons have mild or unrecognized infections that shed virus intermittently in the genital tract. Some cases of first-episode genital herpes are manifested by severe disease that might require hospitalization. Many cases of genital herpes are transmitted by persons who are unaware that they have the infection or are asymptomatic when transmission occurs.

Systemic antiviral drugs partially control the symptoms and signs of herpes episodes when used to treat first clinical episodes or 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 indicate that three antiviral medications provide clinical benefit for genital herpes: acyclovir, valacyclovir, and famciclovir. Valacyclovir is a valine ester of acyclovir with enhanced absorption after oral administration. Famciclovir, a prodrug of penciclovir, also has high oral bioavailability. Topical therapy with acyclovir is substantially less effective than the systemic drug, and its use is discouraged. The recommended acyclovir dosing regimens for both initial and recurrent episodes reflect substantial clinical experience, expert opinion, and FDA-approved dosages.

First Clinical Episode of Genital Herpes

Management of patients with first clinical episode of genital herpes includes antiviral therapy and counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce such transmission. Five percent to 30% of first-episode cases of genital herpes are caused by HSV-1, but clinical recurrences are much less frequent for HSV-1 than HSV-2 genital infection. Therefore, identification of the type of the infecting strain has prognostic importance and may be useful for counseling purposes.

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.

NOTE: Treatment may be extended if healing is incomplete after 10 days of therapy.

Higher dosages of acyclovir (i.e., 400 mg orally five times a day) were used in treatment studies of first-episode herpes proctitis and first-episode oral infection, including stomatitis or pharyngitis. It is unclear whether these forms of mucosal infection require higher doses of acyclovir than used for genital herpes. Valacyclovir and famciclovir probably are also effective for acute HSV proctitis or oral infection, but clinical experience is lacking.

Counseling is an important aspect of managing patients who have genital herpes. 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. Counseling of these patients should include the following:

Recurrent Episodes of HSV Disease

Most patients with first-episode genital HSV-2 infection will have recurrent episodes of genital lesions. Episodic or suppressive antiviral therapy might shorten the duration of lesions or ameliorate recurrences. Because many patients benefit from antiviral therapy, options for treatment should be discussed with all patients.

When treatment is started during the prodrome or within 1 day after onset of lesions, many patients who have recurrent disease benefit from episodic therapy. If episodic treatment of recurrences is chosen, the patient should be provided with antiviral therapy, or a prescription for the medication, so that treatment can be initiated at the first sign of prodrome or genital lesions.

Daily suppressive therapy reduces the frequency of genital herpes recurrences by greater than or equal to 75% among patients who have frequent recurrences (i.e., six or more recurrences per year). Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as 6 years, and with valacyclovir and famciclovir for 1 year. Suppressive therapy has not been associated with emergence of clinically significant acyclovir resistance among immunocompetent patients. After 1 year of continuous suppressive therapy, discontinuation of therapy should be discussed with the patient to assess the patient's psychological adjustment to genital herpes and rate of recurrent episodes, as the frequency of recurrences decreases over time in many patients. Insufficient experience with famciclovir and valacyclovir prevents recommendation of these drugs for greater than 1 year.

Suppressive treatment with acyclovir reduces but does not eliminate asymptomatic viral shedding. Therefore, the extent to which suppressive therapy may prevent HSV transmission is unknown.

Recommended Regimens for Episodic Recurrent Infection

Acyclovir 400 mg orally three times a day for 5 days,

OR

Acyclovir 200 mg orally five times a day for 5 days,

OR

Acyclovir 800 mg orally twice a day for 5 days,

OR

Famciclovir 125 mg orally twice a day for 5 days,

OR

Valacyclovir 500 mg orally twice a day for 5 days.

Recommended Regimens for Daily Suppressive Therapy

Acyclovir 400 mg orally twice a day,

OR

Famciclovir 250 mg orally twice a day,

OR

Valacyclovir 250 mg orally twice a day,

OR

Valacyclovir 500 mg orally once a day,

OR

Valacyclovir 1,000 mg orally once a day.

Valacyclovir 500 mg once a day appears less effective than other valacyclovir dosing regimens in patients who have very frequent recurrences (i.e., greater than or equal to 10 episodes per year). Few comparative studies of valacyclovir and famciclovir with acyclovir have been conducted. The results of these studies suggest that valacyclovir and famciclovir are comparable to acyclovir in clinical outcome. However, valacyclovir and famciclovir may provide increased ease in administration, which is an important consideration for prolonged treatment.

Severe Disease

IV therapy should be provided for patients who have severe disease or complications necessitating hospitalization, such as disseminated infection, pneumonitis, hepatitis, or complications of the central nervous system (e.g., meningitis or encephalitis).

Recommended Regimen

Acyclovir 5-10 mg/kg body weight IV every 8 hours for 5-7 days or until clinical resolution is attained.

Management of Sex Partners

The sex partners of patients who have genital herpes are likely to benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions. However, most persons who have genital HSV infection do not have a history of typical genital lesions. These persons and their future sex partners may benefit from evaluation and counseling. Thus, even asymptomatic sex partners of patients who have newly diagnosed genital herpes should be questioned concerning histories of typical and atypical genital lesions, and they should be encouraged to examine themselves for lesions in the future and seek medical attention promptly if lesions appear.

Most of the available HSV antibody tests do not accurately discriminate between HSV-1 and HSV-2 antibodies, and their use is not currently recommended. Sensitive and type-specific serum antibody assays may become commercially available and contribute to future intervention strategies.

Special Considerations

Allergy, Intolerance, or Adverse Reactions

Allergic and other adverse reactions to acyclovir, valacyclovir, and famciclovir are infrequent. Desensitization to acyclovir has been described previously (23).

HIV Infection

Immunocompromised patients might have prolonged and/or severe episodes of genital or perianal herpes. Lesions caused by HSV are relatively common among HIV-infected patients and may be severe, painful, and atypical. Intermittent or suppressive therapy with oral antiviral agents is often beneficial.

The dosage of antiviral drugs for HIV-infected patients is controversial, but clinical experience strongly suggests that immunocompromised patients benefit from increased doses of antiviral drugs. Regimens such as acyclovir 400 mg orally three to five times a day, as used for other immunocompromised patients, have been useful. Therapy should be continued until clinical resolution is attained. Famciclovir 500 mg twice a day has been effective in decreasing both the rate of recurrences and the rate of subclinical shedding among HIV-infected patients. In immunocompromised patients, valacyclovir in doses of 8 g per day has been associated with a syndrome resembling either hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. However, in the doses recommended for treatment of genital herpes, valacyclovir, acyclovir, and famciclovir probably are safe for use in immunocompromised patients. For severe cases, acyclovir 5 mg/kg IV every 8 hours may be required.

If lesions persist in a patient receiving acyclovir treatment, resistance of the HSV strain to acyclovir should be suspected. Such patients should be managed in consultation with an expert. For severe cases caused by proven or suspected acyclovir-resistant strains, alternate therapy should be administered. All acyclovir-resistant strains are resistant to valacyclovir, and most are resistant to famciclovir. Foscarnet, 40 mg/kg body weight IV every 8 hours until clinical resolution is attained, is often 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.

Pregnancy

The safety of systemic acyclovir and valacyclovir therapy in pregnant women has not been established. Glaxo-Wellcome, Inc., in cooperation with CDC, maintains a registry to assess the use and effects of acyclovir and valacyclovir during pregnancy. Women who receive acyclovir or valacyclovir during pregnancy should be reported to this registry; telephone (800) 722-9292, extension 38465.

Current registry findings do not indicate an increased risk for major birth defects after acyclovir treatment (i.e., in comparison with the general population). These findings provide some assurance in counseling women who have had prenatal exposure to acyclovir. The accumulated case histories represent an insufficient sample for reaching reliable and definitive conclusions regarding the risks associated with acyclovir treatment during pregnancy. Prenatal exposure to valacyclovir and famciclovir is too limited to provide useful information on pregnancy outcomes.

The first clinical episode of genital herpes during pregnancy may be treated with oral acyclovir. In the presence of life-threatening maternal HSV infection (e.g., disseminated infection, encephalitis, pneumonitis, or hepatitis), acyclovir administered IV is indicated. Investigations of acyclovir use among pregnant women suggest that acyclovir treatment near term might reduce the rate of abdominal deliveries among women who have frequently recurring or newly acquired genital herpes by decreasing the incidence of active lesions. However, routine administration of acyclovir to pregnant women who have a history of recurrent genital herpes is not recommended at this time.

Perinatal Infection

Most 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 among women who acquire genital herpes near the time of delivery (30%-50%) and is low among women who have a history of recurrent herpes at term and women who acquire genital HSV during the first half of pregnancy (3%). Therefore, prevention of neonatal herpes should emphasize prevention of acquisition of genital HSV infection during late pregnancy. Susceptible women whose partners have oral or genital HSV infection, or those whose sex partners' infection status is unknown, should be counseled to avoid unprotected genital and oral sexual contact during late pregnancy. The results of viral cultures during pregnancy do not predict viral shedding at the time of delivery, and such cultures are not indicated routinely.

At the onset of labor, all women should be examined and carefully questioned regarding whether they have symptoms of genital herpes. Infants of women who do not have symptoms or signs of genital herpes infection or its prodrome may be delivered vaginally. Abdominal delivery does not completely eliminate the risk for HSV infection in the neonate.

Infants exposed to HSV during birth, as proven by virus isolation or presumed by observation of lesions, should be followed carefully. Some authorities recommend that such infants undergo surveillance cultures of mucosal surfaces to detect HSV infection before development of clinical signs. Available data do not support the routine use of acyclovir for asymptomatic infants exposed during birth through an infected birth canal, because the risk for infection in most infants is low. However, infants born to women who acquired genital herpes near term are at high risk for neonatal herpes, and some experts recommend acyclovir therapy for these infants. Such pregnancies and newborns should be managed in consultation with an expert. All infants who have evidence of neonatal herpes should be promptly evaluated and treated with systemic acyclovir (19). Acyclovir 30-60 mg/kg/day for 10-21 days is the regimen of choice.

Granuloma Inguinale (Donovanosis)

Granuloma inguinale, a rare disease in the United States, is caused by the intracellular Gram-negative bacterium Calymmatobacterium granulomatis. The disease is endemic in certain tropical and developing areas, including India, Papua New Guinea, central Australia, and southern Africa. The disease presents clinically as painless, progressive, ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular (i.e., a beefy red appearance) and bleed easily on contact. The causative organism cannot be cultured on standard microbiologic media, and diagnosis requires visualization of dark-staining Donovan bodies on tissue crush preparation or biopsy. A secondary bacterial infection might develop in the lesions, or the lesions might be coinfected with another sexually transmitted pathogen.

Treatment

Treatment appears to halt progressive destruction of tissue, although prolonged duration of therapy often is required to enable granulation and re-epithelialization of the ulcers. Relapse can occur 6-18 months later despite effective initial therapy.

Recommended Regimens

Trimethoprim-sulfamethoxazole one double-strength tablet orally twice a day for a minimum of 3 weeks,

OR

Doxycycline 100 mg orally twice a day for a minimum of 3 weeks.

Therapy should be continued until all lesions have healed completely.

Alternative Regimens

Ciprofloxacin 750 mg orally twice a day for a minimum of 3 weeks,

OR

Erythromycin base 500 mg orally four times a day for a minimum of 3 weeks.

For any of the above regimens, the addition of an aminoglycoside (gentamicin 1 mg/kg IV every 8 hours) should be considered if lesions do not respond within the first few days of therapy.

Follow-Up

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

Management of Sex Partners

Sex partners of patients who have granuloma inguinale should be examined and treated if they a) had sexual contact with the patient during the 60 days preceding the onset of symptoms in the patient and b) have clinical signs and symptoms of the disease.

Special Considerations

Pregnancy

Pregnancy is a relative contraindication to the use of sulfonamides. Both pregnant and lactating women should be treated with the erythromycin regimen. The addition of a parenteral aminoglycoside (e.g., gentamicin) should be strongly considered.

HIV Infection

HIV-infected persons who have granuloma inguinale should be treated following the regimens cited previously. The addition of a parenteral aminoglycoside (e.g., gentamicin) should be strongly considered.

Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV), a rare disease in the United States, is caused by the invasive serovars L1, L2, or L3 of C. trachomatis. The most frequent clinical manifestation of LGV among heterosexual men is tender inguinal and/or femoral lymphadenopathy that is usually unilateral. Women and homosexually active men might have proctocolitis or inflammatory involvement of perirectal or perianal lymphatic tissues that can result in fistulas and strictures. When most patients seek medical care, they no longer have the self-limited genital ulcer that sometimes occurs at the inoculation site. The diagnosis usually is made serologically and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers.

Treatment

Treatment cures infection and prevents ongoing tissue damage, although tissue reaction can result in scarring. Buboes may 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.

The activity of azithromycin against C. trachomatis suggests that it may be effective in multiple doses over 2-3 weeks, but clinical data regarding its use are lacking.

Follow-Up

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

Management of Sex Partners

Sex partners of patients who have LGV should be examined, tested for urethral or cervical chlamydial infection, and treated if they had sexual contact with the patient during the 30 days preceding onset of symptoms in the patient.

Special Considerations

Pregnancy

Pregnant women should be treated with the erythromycin regimen.

HIV Infection

HIV-infected persons who have LGV should be treated according to the regimens cited previously. Anecdotal evidence suggests that LGV infection in HIV-positive patients may require prolonged therapy and that resolution might be delayed.

Syphilis

General Principles

Background

Syphilis is a systemic disease caused by T. pallidum. Patients who have syphilis may 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 rash, mucocutaneous lesions, and adenopathy), or tertiary infection (i.e., cardiac, neurologic, ophthalmic, auditory, or gummatous lesions). Infections also may be detected by serologic testing during the latent stage. 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 syphilis of unknown duration. Treatment for late latent syphilis, as well as tertiary syphilis, theoretically may require a longer duration of therapy because organisms are dividing more slowly; however, the validity and importance of this concept have not been determined.

Diagnostic Considerations and Use of Serologic Tests

Darkfield examinations and direct fluorescent antibody 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 for syphilis: a) nontreponemal (e.g., Venereal Disease Research Laboratory {VDRL} and RPR) and b) treponemal (e.g., fluorescent treponemal antibody absorbed {FTA-ABS} and microhemagglutination assay for antibody to T. pallidum {MHA-TP}). The use of only one type of test is insufficient for diagnosis because false-positive nontreponemal test results occasionally occur secondary to various medical conditions. 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 to 1:4 or from 1:8 to 1:32), usually is considered necessary to demonstrate a clinically significant difference between two nontreponemal test results that were obtained by using the same serologic test. It is expected that the nontreponemal test will eventually become nonreactive after treatment; however, in some patients, nontreponemal antibodies can persist at a low titer for a long period, sometimes for the remainder of their lives. This response is referred to as the serofast reaction. Most 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 might revert to being serologically nonreactive after 2-3 years. Treponemal test antibody titers correlate poorly with disease activity and should not be used to assess treatment response.

Sequential serologic tests 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, but quantitative results from the two tests cannot be compared directly because RPR titers often are slightly higher than VDRL titers.

HIV-infected patients can have abnormal serologic test results (i.e., unusually high, unusually low, and fluctuating titers). For such patients with clinical syndromes suggestive of early syphilis, use of other tests (e.g., biopsy and direct microscopy) should be considered. However, for most HIV-infected patients, serologic tests appear to be accurate and reliable for the diagnosis of syphilis and for evaluation of treatment response.

No single test can be used to diagnose all cases of neurosyphilis. The diagnosis of neurosyphilis can be made based on various combinations of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, or a reactive VDRL-CSF with or without clinical manifestations. The CSF leukocyte count usually is elevated (greater than 5 WBCs/mm3) when neurosyphilis is present, and it also is a sensitive measure of the effectiveness of therapy. The VDRL-CSF is the standard serologic test for CSF; when reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of neurosyphilis. However, the VDRL-CSF may be nonreactive when neurosyphilis is present. Some experts recommend performing an FTA-ABS test on CSF. The CSF FTA-ABS is less specific (i.e., yields more false-positive results) for neurosyphilis than the VDRL-CSF. However, the test is believed to be highly sensitive, and some experts believe that a negative CSF FTA-ABS test excludes neurosyphilis.

Treatment

Parenteral penicillin G is the preferred drug for treatment of all stages of syphilis. The preparation(s) used (i.e., benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of disease.

The efficacy of penicillin for the treatment of syphilis was well established through clinical experience before the value of randomized controlled clinical trials was recognized. Therefore, almost all the recommendations for the treatment of syphilis are based on expert opinion reinforced by case series, clinical trials, and 50 years of clinical experience.

Parenteral penicillin G is the only therapy with documented efficacy for neurosyphilis or for syphilis during pregnancy. Patients who report a penicillin allergy, including pregnant women with syphilis in any stage and patients with neurosyphilis, should be desensitized and treated with penicillin. Skin testing for penicillin allergy may be useful in some settings (see Management of Patients Who Have a History of Penicillin Allergy), because the minor determinants needed for penicillin skin testing are unavailable commercially.

The Jarisch-Herxheimer reaction is an acute febrile reaction -- often accompanied by headache, myalgia, and other symptoms -- that might occur within the first 24 hours after any therapy for syphilis; patients should be advised of this possible adverse reaction. The Jarisch-Herxheimer reaction often occurs among patients who have early syphilis. Antipyretics may be recommended, but no proven methods prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress among pregnant women. This concern should not prevent or delay therapy (see Syphilis During Pregnancy).

Management of Sex Partners

Sexual transmission of T. pallidum occurs only when mucocutaneous syphilitic lesions are present; such manifestations are uncommon after the first year of infection. However, persons exposed sexually to a patient who has syphilis in any stage should be evaluated clinically and serologically according to the following recommendations:

The time periods before treatment used for identifying at-risk sex partners are a) 3 months plus duration of symptoms for primary syphilis, b) 6 months plus duration of symptoms for secondary syphilis, and c) 1 year for early latent syphilis.

Primary and Secondary Syphilis

Treatment

Parenteral penicillin G has been used effectively for four decades to achieve a local cure (i.e., healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no adequately conducted comparative trials have been performed to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available concerning nonpenicillin regimens.

Recommended Regimen for Adults

Patients who have primary or secondary syphilis should be treated with the following regimen:

Benzathine penicillin G 2.4 million units IM in a single dose.

NOTE: Recommendations for treating pregnant women and HIV-infected patients for syphilis are discussed in separate sections.

Recommended Regimen for Children

After the newborn period, children in whom syphilis is diagnosed should have a CSF examination to detect asymptomatic neurosyphilis, and birth and maternal medical records should be reviewed to assess whether the child has congenital or acquired syphilis (see Congenital Syphilis). Children with acquired primary or secondary syphilis should be evaluated (including consultation with child-protection services) and treated by using the following pediatric regimen (see Sexual Assault or Abuse of Children).

Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose.

Other Management Considerations

All patients who have syphilis should be tested for HIV infection. In geographic areas in which the prevalence of HIV is high, patients who have primary syphilis should be retested for HIV after 3 months if the first HIV test result was negative. This recommendation will become particularly important if it can be demonstrated that intensive antiviral therapy administered soon after HIV seroconversion is beneficial.

Patients who have syphilis and who also have symptoms or signs suggesting neurologic disease (e.g., meningitis) or ophthalmic disease (e.g., uveitis) should be evaluated fully for neurosyphilis and syphilitic eye disease; this evaluation should include CSF analysis and ocular slit-lamp examination. Such patients should be treated appropriately according to the results of this evaluation.

Invasion of CSF by T. pallidum accompanied by CSF abnormalities is common among adults who have primary or secondary syphilis. However, neurosyphilis develops in only a few patients after treatment with the regimens described in this report. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present, lumbar puncture is not recommended for routine evaluation of patients who have primary or secondary syphilis.

Follow-Up

Treatment failures can occur with any regimen. However, assessing response to treatment often is difficult, and no definitive criteria for cure or failure have been established. Serologic test titers may decline more slowly for patients who previously had syphilis. Patients should be reexamined clinically and serologically at both 6 months and 12 months; more frequent evaluation may be prudent if follow-up is uncertain.

Patients who have signs or symptoms that persist or recur or who have a sustained fourfold increase in nontreponemal test titer (i.e., in comparison with either the baseline titer or a subsequent result) probably failed treatment or were reinfected. These patients should be re-treated after reevaluation for HIV infection. Unless reinfection with T. pallidum is certain, a lumbar puncture also should be performed.

Failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis identifies persons at risk for treatment failure. Such persons should be reevaluated for HIV infection. Optimal management of such patients is unclear. At a minimum, these patients should have additional clinical and serologic follow-up. HIV-infected patients should be evaluated more frequently (i.e., at 3-month intervals instead of 6-month intervals). If additional follow-up cannot be ensured, re-treatment is recommended. Some experts recommend CSF examination in such situations.

When patients are re-treated, most experts recommend re-treatment with three weekly injections of benzathine penicillin G 2.4 million units IM, unless CSF examination indicates that neurosyphilis is present.

Management of Sex Partners

Refer to General Principles, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Nonpregnant penicillin-allergic patients who have primary or secondary syphilis should be treated with one of the following regimens. Close follow-up of such patients is essential.

Recommended Regimens

Doxycycline 100 mg orally twice a day for 2 weeks,

OR

Tetracycline 500 mg orally four times a day for 2 weeks.

There is less clinical experience with doxycycline than with tetracycline, but compliance is likely to be better with doxycycline. Therapy for a patient who cannot tolerate either doxycycline or tetracycline should depend on whether the patient's compliance with the therapy regimen and with follow-up examinations can be ensured.

Pharmacologic and bacteriologic considerations suggest that ceftriaxone should be effective, but data concerning ceftriaxone are limited and clinical experience is insufficient to enable identification of late failures. The optimal dose and duration have not been established for ceftriaxone, but a suggested daily regimen of 1 g may be considered if treponemacidal levels in the blood can be maintained for 8-10 days. Single-dose ceftriaxone therapy is not effective for treating syphilis.

For nonpregnant patients whose compliance with therapy and follow-up can be ensured, an alternative regimen is erythromycin 500 mg orally four times a day for 2 weeks. However, erythromycin is less effective than the other recommended regimens.

Patients whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with penicillin. Skin testing for penicillin allergy may be useful in some circumstances in which the reagents and expertise to perform the test adequately are available (see Management of Patients Who Have a History of Penicillin Allergy).

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized, if necessary, and treated with penicillin (see Management of Patients Who Have a History of Penicillin Allergy and Syphilis During Pregnancy).

HIV Infection

Refer to Syphilis in HIV-Infected Persons.

Latent Syphilis

Latent syphilis is defined as those periods after infection with T. pallidum when patients are seroreactive, but demonstrate no other evidence of disease. Patients who have latent syphilis and who acquired syphilis within the preceding year are classified as having early latent syphilis. Patients can be demonstrated as having early latent syphilis if, within the year preceding the evaluation, they had a) a documented seroconversion, b) unequivocal symptoms of primary or secondary syphilis, or c) a sex partner who had primary, secondary, or early latent syphilis. Almost all other patients have latent syphilis of unknown duration and should be managed as if they had late latent syphilis. Nontreponemal serologic titers usually are higher during early latent syphilis than late latent syphilis. However, early latent syphilis cannot be reliably distinguished from late latent syphilis solely on the basis of nontreponemal titers. Regardless of the level of the nontreponemal titers, patients in whom the illness does not meet the definition of early syphilis should be treated as if they have late latent infection. All sexually active women with reactive nontreponemal serologic tests should have a pelvic examination before syphilis staging is completed to evaluate for internal mucosal lesions. All patients who have syphilis should be tested for HIV infection.

Treatment

Treatment of latent syphilis is intended to prevent occurrence or progression of late complications. Although clinical experience supports the effectiveness of penicillin in achieving these goals, limited evidence is available for guidance in choosing specific regimens. There is minimal evidence to support the use of nonpenicillin regimens.

Recommended Regimens for Adults

The following regimens are recommended for nonallergic patients who have normal CSF examinations (if performed):

Early Latent Syphilis:

Benzathine penicillin G 2.4 million units IM in a single dose.

Late Latent Syphilis or Latent Syphilis of Unknown Duration:

Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1-week intervals.

Recommended Regimens for Children

After the newborn period, children in whom syphilis is diagnosed should have a CSF examination to exclude neurosyphilis, and birth and maternal medical records should be reviewed to assess whether the child has congenital or acquired syphilis (see Congenital Syphilis). Older children with acquired latent syphilis should be evaluated as described for adults and treated using the following pediatric regimens (see Sexual Assault or Abuse of Children). These regimens are for non-allergic children who have acquired syphilis and whose results of the CSF examination were normal.

Early Latent Syphilis:

Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose.

Late Latent Syphilis or Latent Syphilis of Unknown Duration:

Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units, administered as three doses at 1-week intervals (total 150,000 units/kg up to the adult total dose of 7.2 million units).

Other Management Considerations

All patients who have latent syphilis should be evaluated clinically for evidence of tertiary disease (e.g., aortitis, neurosyphilis, gumma, and iritis). Patients who have syphilis and who demonstrate any of the following criteria should have a prompt CSF examination:

If dictated by circumstances and patient preferences, a CSF examination may be performed for patients who do not meet these criteria. If a CSF examination is performed and the results indicate abnormalities consistent with neurosyphilis, the patient should be treated for neurosyphilis (see Neurosyphilis).

Follow-Up

Quantitative nontreponemal serologic tests should be repeated at 6, 12, and 24 months. Limited data are available to guide evaluation of the treatment response for patients who have latent syphilis. Patients should be evaluated for neurosyphilis and re-treated appropriately if a) titers increase fourfold, b) an initially high titer (greater than or equal to 1:32) fails to decline at least fourfold (i.e., two dilutions) within 12-24 months, or c) signs or symptoms attributable to syphilis develop in the patient.

Management of Sex Partners

Refer to General Principles, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Nonpregnant patients who have latent syphilis and who are allergic to penicillin should be treated with one of the following regimens.

Recommended Regimens

Doxycycline 100 mg orally twice a day,

OR

Tetracycline 500 mg orally four times a day.

Both drugs should be administered for 2 weeks if the duration of infection is known to have been less than 1 year; otherwise, they should be administered for 4 weeks.

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin (see Management of Patients Who Have a History of Penicillin Allergy and Syphilis During Pregnancy).

HIV Infection

Refer to Syphilis in HIV-Infected Persons.

Tertiary Syphilis

Tertiary syphilis refers to gumma and cardiovascular syphilis, but not to neurosyphilis. Nonallergic patients without evidence of neurosyphilis should be treated with the following regimen.

Recommended Regimen

Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals.

Other Management Considerations

Patients who have symptomatic late syphilis should have a CSF examination before therapy is initiated. Some experts treat all patients who have cardiovascular syphilis with a neurosyphilis regimen. The complete management of patients who have cardiovascular or gummatous syphilis is beyond the scope of these guidelines. These patients should be managed in consultation with an expert.

Follow-Up

Information is lacking with regard to follow-up of patients who have late syphilis. The clinical response depends partially on the nature of the lesions.

Management of Sex Partners

Refer to General Principles, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Patients allergic to penicillin should be treated according to the recommended regimens for late latent syphilis.

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized, if necessary, and treated with penicillin (see Management of Patients Who Have a History of Penicillin Allergy and Syphilis During Pregnancy).

HIV Infection

Refer to Syphilis in HIV-Infected Persons.

Neurosyphilis

Treatment

Central nervous system disease can occur during any stage of syphilis. A patient who has clinical evidence of neurologic involvement with syphilis (e.g., ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis) should have a CSF examination.

Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis; patients with these symptoms should be treated according to the recommendations for neurosyphilis. A CSF examination should be performed for all such patients to identify those with abnormalities who should have follow-up CSF examinations to assess treatment response.

Patients who have neurosyphilis or syphilitic eye disease (e.g., uveitis, neuroretinitis, or optic neuritis) and who are not allergic to penicillin should be treated with the following regimen:

Recommended Regimen

Aqueous crystalline penicillin G 18-24 million units a day, administered as 3-4 million units IV every 4 hours for 10-14 days.

If compliance with therapy can be ensured, patients may be treated with the following alternative regimen:

Alternative Regimen

Procaine penicillin 2.4 million units IM a day, PLUS Probenecid 500 mg orally four times a day, both for 10-14 days.

The durations of the recommended and alternative regimens for neurosyphilis are shorter than that of the regimen used for late syphilis in the absence of neurosyphilis. Therefore, some experts administer benzathine penicillin, 2.4 million units IM, after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy.

Other Management Considerations

Other considerations in the management of patients who have neurosyphilis are as follows:

Follow-Up

If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal. Follow-up CSF examinations also can be used to evaluate changes in the VDRL-CSF or CSF protein after therapy; however, changes in these two parameters are slower, and persistent abnormalities are of less importance. If the cell count has not decreased after 6 months, or if the CSF is not entirely normal after 2 years, re-treatment should be considered.

Management of Sex Partners

Refer to General Principles, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Data have not been collected systematically for evaluation of therapeutic alternatives to penicillin for treatment of neurosyphilis. Patients who report being allergic to penicillin should either be densensitized to penicillin or be managed in consultation with an expert. In some situations, skin testing to confirm penicillin allergy may be useful (see Management of Patients Who Have a History of Penicillin Allergy).

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized, if necessary, and treated with penicillin (see Syphilis During Pregnancy).

HIV Infection

Refer to Syphilis in HIV-Infected Persons.

Syphilis in HIV-Infected Persons

Diagnostic Considerations

Unusual serologic responses have been observed among HIV-infected persons who have syphilis. Most reports involved serologic titers that were higher than expected, but false-negative serologic test results or delayed appearance of seroreactivity also have been reported. Nevertheless, both treponemal and nontreponemal serologic tests for syphilis can be interpreted in the usual manner for most patients who are coinfected with T. pallidum and HIV.

When clinical findings suggest that syphilis is present, but serologic tests are nonreactive or unclear, alternative tests (e.g., biopsy of a lesion, darkfield examination, or direct fluorescent antibody staining of lesion material) may be useful.

Neurosyphilis should be considered in the differential diagnosis of neurologic disease in HIV-infected persons.

Treatment

In comparison with HIV-negative patients, HIV-infected patients who have early syphilis may be at increased risk for neurologic complications and may have higher rates of treatment failure with currently recommended regimens. The magnitude of these risks, although not defined precisely, is probably minimal. No treatment regimens for syphilis are demonstrably more effective in preventing neurosyphilis in HIV-infected patients than the syphilis regimens recommended for HIV-negative patients. Careful follow-up after therapy is essential.

Primary and Secondary Syphilis in HIV-Infected Persons

Treatment

Treatment with benzathine penicillin G, 2.4 million units IM, as for HIV-negative patients, is recommended. Some experts recommend additional treatments (e.g., three weekly doses of benzathine penicillin G as suggested for late syphilis) or other supplemental antibiotics in addition to benzathine penicillin G 2.4 million units IM.

Other Management Considerations

CSF abnormalities often occur among both asymptomatic HIV-infected patients in the absence of syphilis and HIV-negative patients who have primary or secondary syphilis. Such abnormalities in HIV-infected patients who have primary or secondary syphilis are of unknown prognostic significance. Most HIV-infected patients respond appropriately to the currently recommended penicillin therapy; however, some experts recommend CSF examination before therapy and modification of treatment accordingly.

Follow-Up

It is important that HIV-infected patients be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy. Although of unproven benefit, some experts recommend a CSF examination after therapy (i.e., at 6 months).

HIV-infected patients who meet the criteria for treatment failure should be managed the same as HIV-negative patients (i.e., a CSF examination and re-treatment). CSF examination and re-treatment also should be strongly considered for patients whose nontreponemal test titer does not decrease fourfold within 6-12 months. Most experts would re-treat patients with 7.2 million units of benzathine penicillin G (administered as three weekly doses of 2.4 million units each) if CSF examinations are normal.

Special Considerations

Penicillin Allergy

Penicillin-allergic patients who have primary or secondary syphilis and HIV infection should be managed according to the recommendations for penicillin-allergic HIV-negative patients.

Latent Syphilis in HIV-Infected Persons

Diagnostic Considerations

HIV-infected patients who have early latent syphilis should be managed and treated according to the recommendations for HIV-negative patients who have primary and secondary syphilis.

HIV-infected patients who have either late latent syphilis or syphilis of unknown duration should have a CSF examination before treatment.

Treatment

A patient with late latent syphilis or syphilis of unknown duration and a normal CSF examination can be treated with 7.2 million units of benzathine penicillin G (as three weekly doses of 2.4 million units each). Patients who have CSF consistent with neurosyphilis should be treated and managed as described for neurosyphilis (see Neurosyphilis).

Follow-Up

Patients should be evaluated clinically and serologically at 6, 12, 18, and 24 months after therapy. If, at any time, clinical symptoms develop or nontreponemal titers rise fourfold, a repeat CSF examination should be performed and treatment administered accordingly. If between 12 and 24 months the nontreponemal titer fails to decline fourfold, the CSF examination should be repeated, and treatment administered accordingly.

Special Considerations

Penicillin Allergy

Penicillin regimens should be used to treat all stages of syphilis in HIV-infected patients. Skin testing to confirm penicillin allergy may be used (see Management of Patients Who Have a History of Penicillin Allergy). Patients may be desensitized, then treated with penicillin.

Syphilis During Pregnancy

All women should be screened serologically for syphilis during the early stages of pregnancy. In populations in which utilization of prenatal care is not optimal, RPR-card test screening and treatment (i.e., if the RPR-card test is reactive) should be performed at the time a pregnancy is diagnosed. For communities and populations in which the prevalence of syphilis is high or for patients at high risk, serologic testing should be performed twice during the third trimester, at 28 weeks of gestation and at delivery. (Some states mandate screening at delivery for all women.) Any woman who delivers a stillborn infant after 20 weeks of gestation should be tested for syphilis. No infant should leave the hospital without the maternal serologic status having been determined at least once during pregnancy.

Diagnostic Considerations

Seropositive pregnant women should be considered infected unless an adequate treatment history is documented clearly in the medical records and sequential serologic antibody titers have declined.

Treatment

Penicillin is effective for preventing maternal transmission to the fetus and for treating fetal-established infection. Evidence is insufficient to determine whether the specific, recommended penicillin regimens are optimal.

Recommended Regimens

Treatment during pregnancy should be the penicillin regimen appropriate for the stage of syphilis.

Other Management Considerations

Some experts recommend additional therapy in some settings. A second dose of benzathine penicillin 2.4 million units IM may be administered 1 week after the initial dose for women who have primary, secondary, or early latent syphilis. Ultrasonographic signs of fetal syphilis (i.e., hepatomegaly and hydrops) indicate a greater risk for fetal treatment failure; such cases should be managed in consultation with obstetric specialists.

Women treated for syphilis during the second half of pregnancy are at risk for premature labor and/or fetal distress if the treatment precipitates the Jarisch-Herxheimer reaction. These women should be advised to seek obstetric attention after treatment if they notice any contractions or decrease in fetal movements. Stillbirth is a rare complication of treatment, but concern for this complication should not delay necessary treatment. All patients who have syphilis should be offered testing for HIV infection.

Follow-Up

Coordinated prenatal care and treatment follow-up are important, and syphilis case management may help facilitate prenatal enrollment. Serologic titers should be repeated in the third trimester and at delivery. Serologic titers may be checked monthly in women at high risk for reinfection or in geographic areas in which the prevalence of syphilis is high. The clinical and antibody response should be appropriate for the stage of disease. Most women will deliver before their serologic response to treatment can be assessed definitively.

Management of Sex Partners

Refer to General Principles, Management of Sex Partners.

Special Considerations

Penicillin Allergy

There are no proven alternatives to penicillin for treatment of syphilis during pregnancy. Pregnant women who have a history of penicillin allergy should be desensitized and treated with penicillin. Skin testing may be helpful (see Management of Patients Who Have a History of Penicillin Allergy).

Tetracycline and doxycycline usually are not used during pregnancy. Erythromycin should not be used, because it does not reliably cure an infected fetus. Data are insufficient to recommend azithromycin or ceftriaxone.

HIV Infection

Refer to Syphilis in HIV-Infected Persons.


CONGENITAL SYPHILIS

Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and, therefore, on the routine serologic screening of pregnant women at the time of the first prenatal visit. Serologic testing and a sexual history also should be obtained at 28 weeks of gestation and at delivery in communities and populations in which the risk for congenital syphilis is high. Moreover, as part of the management of pregnant women who have syphilis, information concerning treatment of sex partners should be obtained in order to assess possible maternal reinfection. All pregnant women who have syphilis should be tested for HIV infection.

Routine screening of newborn sera or umbilical cord blood is not recommended. Serologic testing of the mother's serum is preferred to testing infant serum, because the serologic tests performed on infant serum can be nonreactive if the mother's serologic test result is of low titer or if the mother was infected late in pregnancy. No infant should leave the hospital without the maternal serologic status having been documented at least once during pregnancy.

Evaluation and Treatment of Infants During the First Month of Life

Diagnostic Considerations

The diagnosis of congenital syphilis is complicated by the transplacental transfer of maternal nontreponemal and treponemal IgG antibodies to the fetus. This transfer of antibodies makes the interpretation of reactive serologic tests for syphilis in infants difficult. Treatment decisions often must be made based on a) identification of syphilis in the mother; b) adequacy of maternal treatment; c) presence of clinical, laboratory, or radiographic evidence of syphilis in the infant; and d) comparison of the infant's nontreponemal serologic test results with those of the mother.

Who Should Be Evaluated

All infants born to seroreactive mothers should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on infant serum (i.e., umbilical cord blood might be contaminated with maternal blood and might yield a false-positive result). A treponemal test (i.e., MHA-TP or FTA-ABS) of a newborn's serum is not necessary.

Evaluation

All infants born to women who have reactive serologic tests for syphilis should be examined thoroughly for evidence of congenital syphilis (e.g., nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, and/or pseudoparalysis of an extremity). Pathologic examination of the placenta or umbilical cord using specific fluorescent antitreponemal antibody staining is suggested. Darkfield microscopic examination or direct fluorescent antibody staining of suspicious lesions or body fluids (e.g., nasal discharge) also should be performed.

Further evaluation of the infant is dependent on a) whether any abnormalities are present on physical examination, b) maternal treatment history, c) stage of infection at the time of treatment, and d) comparison of maternal (at delivery) and infant nontreponemal titers utilizing the same test and preferably the same laboratory.

Treatment

Infants should be treated for presumed congenital syphilis if they were born to mothers who met any of the following criteria:

Regardless of a maternal history of infection with T. pallidum or treatment for syphilis, the evaluation should include the following tests if the infant has either a) an abnormal physical examination that is consistent with congenital syphilis, b) a serum quantitative nontreponemal serologic titer that is fourfold greater than the mother's titer, or c) a positive darkfield or fluorescent antibody test of body fluid(s).

Recommended Regimens

Aqueous crystalline penicillin G 100,000-150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life, and every 8 hours thereafter for a total of 10 days;

OR

Procaine penicillin G 50,000 units/kg/dose IM a day in a single dose for 10 days.

If greater than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy.

In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant. For infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer, the evaluation depends on the maternal treatment history and stage of infection.

This page last reviewed: Friday, July 13, 2007
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