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Sexually Transmitted Diseases Treatment Guidelines --- 2002Prepared by The material in this report was prepared for publication by the National Center for HIV, STD, and TB Prevention, Harold W. Jaffe, M.D., Acting Director; and the Division of Sexually Transmitted Diseases Prevention, Harold W. Jaffe, M.D., Acting Director. SummaryThese guidelines for the treatment of patients who have sexually transmitted diseases (STDs) were developed by the Centers for Disease Control and Prevention (CDC) after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on September 26--28, 2000. The information in this report updates the 1998 Guidelines for Treatment of Sexually Transmitted Diseases (MMWR 1998;47[No. RR-1]). Included in these updated guidelines are new alternative regimens for scabies, bacterial vaginosis, early syphilis, and granuloma inguinale; an expanded section on the diagnosis of genital herpes (including type-specific serologic tests); new recommendations for treatment of recurrent genital herpes among persons infected with human immunodeficiency virus (HIV); a revised approach to the management of victims of sexual assault; expanded regimens for the treatment of urethral meatal warts; and inclusion of hepatitis C as a sexually transmitted infection. In addition, these guidelines emphasize education and counseling for persons infected with human papillomavirus, clarify the diagnostic evaluation of congenital syphilis, and present information regarding the emergence of quinolone-resistant Neisseria gonorrhoeae and implications for treatment. Recommendations also are provided for vaccine-preventable STDs, including hepatitis A and hepatitis B. IntroductionPhysicians and other health-care providers play a critical role in preventing and treating sexually transmitted diseases (STDs). These recommendations for the treatment of STDs are intended to assist with that effort. Although these guidelines emphasize treatment, prevention strategies and diagnostic recommendations also are discussed. This report was produced through a multi-stage process. Beginning in 2000, CDC personnel and professionals knowledgeable in the field of STDs systematically reviewed literature (i.e., published abstracts and peer-reviewed journal articles) concerning each of the major STDs, focusing on information that had become available since publication of the 1998 Guidelines for Treatment of Sexually Transmitted Diseases (1). 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. A draft document was developed on the basis of the reviews. In September 2000, CDC staff members and invited consultants assembled in Atlanta for a 3-day meeting to present the key questions regarding STD treatment that emerged from the literature reviews and the information available to answer those questions. When relevant, the questions focused on four principal outcomes of STD therapy for each individual disease: 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 [DOT]) of specific regimens also were discussed. The consultants then assessed whether the questions identified were relevant, ranked them in order of priority, and attempted to arrive at answers using the available evidence. In addition, the consultants evaluated the quality of evidence supporting the answers on the basis of the number, type, and quality of the studies. In several areas, the process diverged from that previously described. The sections concerning adolescents and hepatitis A, B, and C infections were developed by other CDC staff members knowledgeable in this field. The recommendations for STD screening during pregnancy were developed after CDC staff reviewed the published recommendations from other knowledgeable groups. The sections concerning early human immunodeficiency virus (HIV) infection are a compilation of recommendations developed by CDC staff members knowledgeable in the field of HIV infection. The sections on hepatitis B virus (HBV) (2) and hepatitis A virus (HAV) (3) 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 a supplement issue of the journal Clinical Infectious Diseases. When more than one therapeutic regimen is recommended, the sequence is alphabetized unless the choices for therapy are prioritized based on efficacy, convenience, or cost. For STDs with more than one recommended regimen, almost all regimens have similar efficacy and similar rates of intolerance or toxicity unless otherwise specified. These recommendations were developed in consultation with public- and private-sector professionals knowledgeable in the treatment of patients with STDs. They are applicable to various 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 guidelines 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 Prevention GuidelinesThe prevention and control of STDs is based on the following five major concepts: a) education and counseling of persons at risk on ways to adopt safer sexual behavior; b) identification of asymptomatically infected persons and of symptomatic persons unlikely to seek diagnostic and treatment services; c) effective diagnosis and treatment of infected persons; d) evaluation, treatment, and counseling of sex partners of persons who are infected with an STD; and e) preexposure vaccination of persons at risk for vaccine-preventable STDs. Although this report focuses mainly on the clinical aspects of STD control, primary prevention of STDs begins with changing the sexual behaviors that place persons at risk for infection. Moreover, because STD control activities reduce the likelihood of transmission to sex partners, treatment of infected persons constitutes primary prevention of spread within the community. Clinicians have a unique opportunity to provide education and counseling to their patients. As part of the clinical interview, health-care providers can obtain sexual histories from their patients. Guidance in obtaining a sexual history is available in Contraceptive Technology, 17th edition (4). Prevention MessagesPrevention 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). If risk factors are identified, providers should encourage patients to adopt safer sexual behaviors. Counseling skills (e.g., respect, compassion, and a nonjudgmental attitude) are essential to the effective delivery of prevention messages. Techniques that can be effective in facilitating rapport with the patient include using open-ended questions, using understandable language, and reassuring the patient that treatment will be provided regardless of circumstances unique to individual patients (including ability to pay, citizenship or immigration status, language spoken, or lifestyle). Many patients seeking treatment or screening for STDs expect evaluation for all common STDs; all patients should be specifically informed if testing for a common STD (e.g., genital herpes and human papillomavirus [HPV]) is not performed. Sexual Transmission The most reliable way to avoid transmission of STDs is to abstain from sexual intercourse (i.e., oral, vaginal, or anal sex) or to be in a long-term, mutually monogamous relationship with an uninfected partner. Counseling that encourages abstinence from sexual intercourse is crucial for persons who are being treated for an STD or whose partners are undergoing treatment and for persons who wish to avoid the possible consequences of sexual intercourse (e.g., STD/HIV and unintended pregnancy). A more comprehensive discussion of abstinence and the range of sexual expression is available in Contraceptive Technology, 17th edition (4).
Preexposure Vaccination Preexposure vaccination is one of the most effective methods for preventing transmission of certain STDs. For example, because hepatitis B virus infection frequently is sexually transmitted, hepatitis B vaccination is recommended for all unvaccinated persons being evaluated for an STD. In addition, hepatitis A vaccine is currently licensed and is recommended for men who have sex with men (MSM) and illegal drug users (both injection and non-injection). Vaccine trials for other STDs are being conducted, and additional vaccines may become available in the next several years. Prevention MethodsMale Condoms When used consistently and correctly, male latex condoms are effective in preventing the sexual transmission of HIV infection and can reduce the risk for other STDs (i.e., gonorrhea, chlamydia, and trichomonas). However, because condoms do not cover all exposed areas, they are likely to be more effective in preventing infections transmitted by fluids from mucosal surfaces (e.g., gonorrhea, chlamydia, trichomoniasis, and HIV) than in preventing those transmitted by skin-to-skin contact (e.g., herpes simplex virus [HSV], HPV, syphilis, and chancroid). 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., approximately two broken condoms per 100 condoms used). Condom failure usually results from inconsistent or incorrect use rather than condom breakage. Male condoms made of materials other than latex are available in the United States. Although they have had higher breakage and slippage rates when compared with latex condoms, the pregnancy rates among women whose partners use these condoms are similar. Non-latex condoms (i.e., those made of polyurethane or other synthetic material) can be substituted for persons with latex allergy. Patients should be advised that condoms must be used consistently and correctly to be highly effective in preventing STDs. Patients 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™), which consists of a lubricated polyurethane sheath with a ring on each end that is inserted into the vagina, is an effective mechanical barrier to viruses, including HIV (5). With the exception of 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 may substantially reduce the risk for STDs. When a male condom cannot be used properly, sex partners should consider using a female condom. Vaginal Spermicides, Sponges, and Diaphragms Recent evidence has indicated that vaginal spermicides containing nonoxynol-9 (N-9) are not effective in preventing cervical gonorrhea, chlamydia, or HIV infection (6). Thus, spermicides alone are not recommended for STD/HIV prevention. Frequent use of spermicides containing N-9 has been associated with genital lesions, which may be associated with an increased risk of HIV transmission. The vaginal contraceptive sponge appears to protect 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 (7). Neither vaginal sponges nor diaphragms should be relied on to protect women against HIV infection. The role of spermicides, sponges, and diaphragms for preventing transmission of HIV to men has not been evaluated. Diaphragm and spermicide use has been associated with an increased risk of bacterial urinary tract infection in women. Condoms and N-9 Vaginal Spermicides Condoms lubricated with spermicides are no more effective than other lubricated condoms in protecting against the transmission of HIV and other STDs. Distribution of previously purchased condoms lubricated with N-9 spermicide should continue provided the condoms have not passed their expiration date. However, purchase of any additional condoms lubricated with the spermicide N-9 is not recommended because spermicide-coated condoms cost more, have a shorter shelf-life than other lubricated condoms, and have been associated with urinary tract infection in young women. Rectal Use of N-9 Spermicides Recent data indicate that N-9 may increase the risk for HIV transmission during vaginal intercourse (6). Although similar studies have not been conducted among men who use N-9 spermicide during anal intercourse with other men, N-9 can damage the cells lining the rectum, thus providing a portal of entry for HIV and other sexually transmissible agents. Therefore, N-9 should not be used as a microbicide or lubricant during anal intercourse. Nonbarrier Contraception, Surgical Sterilization, and Hysterectomy Women who are not at risk for pregnancy might incorrectly perceive themselves to be at no risk for STDs, including HIV infection. Contraceptive methods that are not mechanical or chemical barriers offer no protection against HIV or other STDs. Women who use hormonal contraception (e.g., oral contraceptives, Norplant™, and Depo-Provera™), have intrauterine devices (IUDs), have been surgically sterilized, or have had hysterectomies should be counseled regarding the use of condoms and the risk for STDs, including HIV infection. STD/HIV Prevention CounselingInteractive counseling approaches directed at a patient's personal risk, the situations in which risk occurs, and use of goal-setting strategies are effective in STD prevention (8). One such approach --- "client-centered" HIV prevention counseling --- involves two sessions, each lasting 15--20 minutes, and has been recommended for STD clinic patients who receive HIV testing. In addition to prevention counseling, certain videos and large group presentations that provide explicit information about how to use condoms correctly have been effective in reducing the occurrence of additional STDs among persons at high risk, including STD clinic patients and adolescents. Results from randomized controlled trials demonstrate that compared with traditional approaches to providing information, certain brief risk reduction counseling approaches can reduce the occurrence of new sexually transmitted infections by 25%--40% among STD clinic patients (9). Interactive counseling strategies can be effectively used by most health-care providers, regardless of educational background or demographic profile. High-quality counseling is best ensured when clinicians are provided basic training in prevention counseling methods and skills building approaches, periodic supervisor observation of counseling with immediate feedback to counselors, periodic counselor and/or patient satisfaction evaluations, and regularly scheduled meetings of counselors and supervisors to discuss difficult situations. Prevention counseling is believed to be more effective if provided in a non-judgmental manner appropriate to the patient's culture, language, sex, sexual orientation, age, and developmental level. Partner NotificationPartner notification, once referred to as "contact tracing" but more recently included in the broader category of partner services, is the process of learning from persons with STDs about their sexual partners and helping to arrange for evaluation and treatment of those partners. Providers can furnish this service directly or with assistance from state and local health departments. The intensity of services and the specific conditions for which such services are offered by health agencies vary from area to area. Such services usually are accompanied by health counseling and may include referral of patients and their partners for other services. Many persons benefit from partner notification; thus, providers should encourage their patients to make partners aware of potential STD risk and urge them to seek diagnosis and treatment, regardless of assistance from local health agencies. However, whether the process of partner notification effectively decreases exposure to STDs from a person's sexual environment or whether it changes the incidence and prevalence of disease is uncertain. The paucity of supporting evidence regarding the consequences of partner notification has spurred the exploration of alternative approaches. One such approach is to place partner notification in the larger context of the sexual and social networks in which people are exposed to STDs. The underlying hypotheses are that networks have an influence on disease transmission that is independent of personal behaviors, that network structure is related directly to prevalence and to underlying disease transmission dynamics, and that network approaches provide a more powerful tool for identifying exposed persons and other persons at risk. A second such approach for which supporting data are being collected is the use of patient delivered therapy for treatment of contacts and others at risk, a technique that can considerably expand the role of practitioners in the control of STDs. The combination of these approaches has the potential to provide both an intervention and its evaluative tool. These approaches have not yet been sufficiently assessed to warrant definitive recommendations. However, practitioners and public health professionals should be aware of the current potential use of these nontraditional modalities in the prevention and control of STDs. Reporting and ConfidentialityThe 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, chlamydia, and AIDS are reportable diseases in every state. HIV infection and chancroid are reportable in many states. The requirements for reporting other STDs differ by state, and clinicians should be familiar with local reporting requirements. Reporting can 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 kept strictly confidential. In most jurisdictions, such reports are protected by statute from subpoena. Before public health representatives conduct a follow-up of a positive STD-test result, they should consult the patient's health-care provider to verify the diagnosis and treatment. Special PopulationsPregnant WomenIntrauterine or perinatally transmitted STDs can have severely debilitating effects on pregnant women, their partners, and their fetuses. All pregnant women and their sex partners should be asked about STDs, counseled about the possibility of perinatal infections, and ensured access to treatment, if needed. Recommended Screening Tests
Other Concerns Other STD-related concerns are as follows.
For a more detailed discussion of these guidelines, as well as infections not transmitted sexually, refer to the following references: Guide to Clinical Preventive Services (10), Guidelines for Perinatal Care (11), American College of Obstetricians and Gynecologists (ACOG) Educational Bulletin: Antimicrobial Therapy for Obstetric Patients (12), ACOG Committee Opinion: Primary and Preventive Care: Periodic Assessments (13), Recommendations for the Prevention and Management of Chlamydia trachomatis Infections (14), 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), Mother-to-infant transmission of hepatitis C virus (15), Hepatitis C: Screening in pregnancy (16), American College of Obstetricians and Gynecologists (ACOG) Educational Bulletin: Viral hepatitis in pregnancy (17), Human Immunodeficiency Virus Screening: Joint statement of the AAP and ACOG (18), Preventing Perinatal Transmission of HIV (19), and the Revised Public Health Service Recommendations for HIV Screening of Pregnant Women (20). These sources are not entirely consistent 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 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. AdolescentsHealth professionals who provide care for adolescents should be aware of several issues that relate specifically to persons within this age group. The rates of many STDs are highest among adolescents. For example, the reported rates of chlamydia and gonorrhea are highest among females aged 15--19 years, and young adults are also at highest risk for HPV infection. In addition, surveillance data indicate that 9% of adolescents who have acute HBV infection either have had sexual contact with a chronically infected person or with multiple sex partners or report 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 (1). Younger adolescents (i.e., persons aged <15 years) who are sexually active are at particular risk for infection. Adolescents at especially high risk for STDs include youth in detention facilities, STD clinic patients, male homosexuals, and injection-drug users. Adolescents are at greater risk for STDs because they frequently have unprotected intercourse, are biologically more susceptible to infection, are engaged in partnerships often of limited duration, 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 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 thus prevent the establishment of patterns of behavior that can undermine sexual health. With a few 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. Health-care providers should acknowledge the importance of confidentiality for adolescents and should strive to follow policies that comply with state laws to ensure the confidentiality of STD-related services. Despite the prevalence of STDs among adolescents, providers frequently fail to inquire about sexual behavior, assess risk for STDs, counsel about risk reduction, and screen for asymptomatic infection during clinical encounters. When addressing these sensitive areas with young people, 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 (e.g., sex and drug-use behaviors). Careful counseling and thorough discussions are particularly important for adolescents who may not acknowledge that they engage in high-risk behaviors. Care and counseling should be direct and nonjudgmental. ChildrenManagement of children who have STDs requires close cooperation between clinicians, 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 (e.g., HPV infection and vaginitis), the association with sexual contact is not as clear (see Sexual Assault and STDs). Men Who Have Sex with MenSome MSM are at high risk for HIV infection and other viral and bacterial STDs. Although the frequency of unsafe sexual practices and reported rates of bacterial STDs and incident HIV infection has declined substantially in MSM during the last several decades, increased rates of infectious syphilis, gonorrhea, and chlamydial infection, largely among HIV-infected MSM, have been recently reported in many cities in the United States and other industrialized countries. Preliminary data also indicate higher frequencies of unsafe sex and suggest that the incidence of HIV infection may be rising among MSM in some cities. The underlying behavioral changes likely are related to effects of improved HIV/AIDS therapy on quality of life and survival, "safer sex burnout," and in some cities, adverse trends in substance abuse. Clinicians should assess sexual risk for all male patients, which includes routinely inquiring about the sex of patients' sex partners. MSM, including those with HIV infection, should routinely undergo straightforward, nonjudgmental STD/HIV risk assessment and client-centered prevention counseling to reduce the likelihood of acquisition or transmission of HIV and other STDs. In addition, screening for STDs should be considered for many MSM. The following screening recommendations are based on preliminary data; these tests should be performed at least annually for sexually active MSM:
In addition, vaccination against hepatitis is the most effective means of preventing sexual transmission of hepatitis A and B. Prevaccination serologic testing may be cost-effective in MSM, among whom the prevalence of hepatitis A and B infection is likely to be high. More frequent STD screening (e.g., at 3--6-month intervals) may be indicated for MSM at highest risk (e.g., those who acknowledge having multiple anonymous partners or having sex in conjunction with illicit drug use and patients whose sex partners participate in these activities). Screening tests usually are indicated regardless of a patient's history of consistent use of condoms for insertive or receptive anal intercourse. Providers also should be knowledgeable about the common manifestations of symptomatic STDs in MSM (e.g., urethral discharge, dysuria, anorectal symptoms [such as pain, pruritis, discharge, and bleeding], genital or anorectal ulcers, other mucocutaneous lesions, lymphadenopathy, and skin rash). If these symptoms are present, providers should perform appropriate diagnostic tests. HIV Infection: Detection, Counseling, and ReferralInfection with HIV produces a spectrum of disease that progresses from a clinically latent or asymptomatic state to AIDS as a late manifestation. The pace of disease progression varies. In untreated patients, the time between infection with HIV and the development of AIDS ranges from a few months to as long as 17 years (median: 10 years). Most adults and adolescents infected with HIV remain symptom-free for extended periods, but viral replication is active during all stages of infection, increasing substantially as the immune system deteriorates. In the absence of treatment, AIDS eventually develops in almost all HIV-infected persons; in one study of HIV-infected adults, AIDS developed in 87% within 17 years of infection. Additional cases are expected to occur among those who have remained AIDS-free for longer periods of time. 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. Prompt diagnosis of HIV infection is important for several reasons. Treatments are available that slow the decline of immune system function; use of these therapies has been associated with substantial declines in HIV-associated morbidity and mortality in recent years. HIV-infected persons who have altered immune function are at increased risk for infections for which preventive measures are available (e.g., Pneumocystis 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 health-care providers to counsel such patients, refer them to various support services, and help prevent 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, many services are often 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 STD treatment facilities, HIV-infected patients should be educated about HIV infection and the various options for available support services and HIV care. Because multiple, complex services are required for management of HIV infection, detailed information (particularly regarding medical care) is beyond the scope of this section and can be found elsewhere (8,21). This report provides information regarding diagnostic testing for HIV infection, counseling patients who have HIV infection, and referral of patients to support services (including medical care). Information also is provided regarding the management of sex partners, because such services can and should be provided in STD treatment facilities. In addition, the topics of HIV infection during pregnancy and in infants and children are addressed. Detection of HIV Infection: Diagnostic TestingTesting for HIV is recommended and should be offered to all 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 tests for antibodies against HIV-1 and HIV-2 (HIV-1/2). Antibody testing begins with a sensitive screening test (e.g., the enzyme immunoassay [EIA]). Reactive screening tests must be confirmed by supplemental test (e.g., 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 3 months after infection. Although a negative antibody test result usually indicates that a person is not infected, antibody tests cannot exclude recent infection. Most HIV infections in the United States are caused by HIV-1; <100 cases of HIV-2 infection have been documented (22). However, HIV-2 infection should be suspected in persons who have epidemiologic risk factors for HIV-2. Examples of these risk factors include persons with sex partners from West Africa (where HIV-2 is endemic), those with sex partners known to be infected with HIV-2, and persons who received a blood transfusion or a non-sterile injection in a West African country. HIV-2 testing is also indicated when clinical evidence of HIV exists but tests for antibodies to HIV-1 are not positive, or when HIV-1 Western blot results include the unusual indeterminate pattern of gag plus pol bands in the absence of env bands (22). Health-care providers should be knowledgeable about the symptoms and signs of acute retroviral syndrome, which is characterized by fever, malaise, lymphadenopathy, and skin rash. This syndrome frequently occurs in the first few weeks after HIV infection, before antibody test results become positive. Suspicion of acute retroviral syndrome should prompt nucleic acid testing (HIV plasma RNA [i.e., viral load]) to detect the presence of HIV, although this test is not approved for diagnostic purposes; a positive test should be confirmed by another HIV test. Current guidelines suggest that persons with recently acquired HIV infection might benefit from antiretroviral drugs, and such patients may be candidates for clinical trials (23,24). Therefore, patients with acute HIV infection should be referred immediately to an HIV clinical care provider. Detection of HIV infection should prompt efforts to reduce the risk behavior that resulted in HIV infection and could result in transmission of HIV to others. Early counseling and education are particularly important for persons with recently acquired infection, because HIV plasma RNA levels are characteristically high during this phase of infection and likely constitute a risk factor for HIV transmission. The following are specific recommendations for diagnostic testing for HIV infection.
Counseling for Patients with HIV Infection and Referral to Support ServicesPatients can be expected to be distressed when first informed of a positive HIV test result. Such patients face several major adaptive challenges, including 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 possible employment or housing discrimination. Therefore, in addition to medical care, 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. A comprehensive discussion of specific recommendations is available in the Guidelines for HIV Counseling, Testing, and Referral (8). 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 to avoid fragmentation of care. Although a single source that is capable of providing comprehensive care for all stages of HIV infection is preferred, the limited availability of such resources often results in the need to coordinate care among medical and social service providers in different locations. Providers should avoid long delays between diagnosis of HIV infection and access to additional medical and psychosocial services. Recently identified HIV infection may not have been recently acquired. Persons newly diagnosed with HIV may be at any stage of infection. Therefore, health-care providers should be alert for symptoms or signs that suggest advanced HIV infection (e.g., fever, weight loss, diarrhea, cough, shortness of breath, and oral candidiasis). The presence of any of these symptoms should prompt urgent referral for medical care. Similarly, providers should be alert for signs of psychologic distress and be prepared to refer patients accordingly. Diagnosis of HIV infection reinforces the need to counsel patients regarding high risk behaviors, because the consequences of such behaviors include the risk for acquiring additional STDs and for transmitting HIV (and other STDs) to other persons. Such attention to behaviors in HIV-infected persons is consistent with national strategies for HIV prevention (25). Providers should be able to refer patients for prevention counseling and risk reduction support concerning high risk behaviors (e.g., substance abuse and high risk sexual behavior). HIV-infected patients in the STD treatment setting should be educated about what to expect as they enter medical care for HIV infection. In non-emergent situations, the initial evaluation of HIV-positive patients usually includes a) a detailed medical history, including sexual and substance-abuse history, previous STDs, and specific HIV-related symptoms or diagnoses; b) a physical examination (including a gynecologic examination for women); c) testing for N. gonorrhoeae and C. trachomatis (and for women, a Pap test and wet mount examination of vaginal secretions); d) complete blood and platelet counts and blood chemistry profile; e) toxoplasma antibody test; f) tests for hepatitis B, C, and for MSM, hepatitis A; g) syphilis serology; h) a CD4+ T-lymphocyte analysis and determination of HIV plasma RNA (i.e., HIV viral load); i) a tuberculin skin test (TST) (sometimes referred to as a purified protein derivative [PPD]); j) a urinalysis; and k) a chest radiograph (21). In subsequent visits, once the results of laboratory and skin tests are available, the patient may be offered antiretroviral therapy (23,24), if indicated, as well as specific medications to reduce the incidence of opportunistic infections (e.g., PCP, TE, disseminated MAC infection, and TB) (21,26). Hepatitis B vaccination should be offered to patients who lack hepatitis B serologic markers. Hepatitis A vaccination should be given to persons at increased risk for hepatitis A infection (e.g., MSM and illegal drug users) and to patients with chronic hepatitis B or hepatitis C who lack antibodies to hepatitis A. Influenza vaccination should be offered annually, and pneumococcal vaccination should be administered if not given in the previous 5 years (21). Providers must be alert to the possibility of new or recurrent STDs and treat such conditions aggressively. Occurrence of an STD in an HIV-infected person is an indication of high-risk behavior and should prompt referral for counseling. Because many STDs are asymptomatic, routine screening for curable STDs (e.g., syphilis, gonorrhea, and chlamydia) should be performed at least yearly for sexually active persons. More frequent screening may be appropriate depending on individual risk behaviors, the local epidemiology of STDs, and whether incident STDs are detected by screening or by the presence of symptoms. Patients should receive, or be referred for, a thorough psychosocial evaluation, including ascertainment of behavioral factors indicating risk for transmitting HIV. Patients may require referral for specific behavioral intervention (e.g., a substance abuse program), for mental health disorders (e.g., depression), or for emotional distress. They may require assistance with securing and maintaining employment and housing. Women should be counseled or appropriately referred regarding reproductive choices and contraceptive options. Patients with multiple psychosocial problems may be candidates for prevention case management (27). The following are specific recommendations for counseling and referral.
Management of Sex Partners and Injection-Drug PartnersClinicians evaluating HIV-infected persons should collect information to determine whether any partners should be notified about possible exposure to HIV (8). When referring to persons who are infected with HIV, the term "partner" includes not only sex partners but also injection-drug users who share syringes or other injection equipment. The rationale for partner notification is that the early diagnosis and treatment of HIV infection in these partners possibly reduces morbidity and provides the opportunity to encourage risk-reducing behaviors. Partner notification for HIV infection must be confidential and depends on the 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 confidentiality 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 following are specific recommendations for implementing partner-notification procedures.
Special ConsiderationsPregnancy Voluntary counseling and HIV testing should be offered routinely to all pregnant women as early in pregnancy as possible (20). For women who decline these services, providers should continue to strongly encourage testing and to address concerns that pose obstacles to testing. Providing pregnant women with counseling and testing is particularly important not only to maintain the health of the patient, but also because interventions (antiretroviral and obstetrical) are available that can reduce perinatal transmission of HIV. Once identified as being HIV-infected, pregnant women should be informed specifically about the risk for perinatal infection. Current evidence indicates that, in the absence of antiretroviral and other interventions, 15%--25% of infants born to HIV-infected mothers will become infected with HIV; such evidence also indicates that an additional 12%--14% are infected during breastfeeding in resource-limited settings where HIV-infected women breastfeed their infants into the second year of life (28). However, the risk of HIV transmission can be reduced substantially to <2% through antiretroviral regimens and obstetrical interventions (i.e., AZT or nevirapine and elective c-section at 38 weeks of pregnancy) and by avoiding breastfeeding (29). Pregnant women who are HIV-infected should be counseled about their options (either on-site or by referral), given appropriate antenatal treatment, and (for women living in the United States, where infant formula is readily available and can be safely prepared) advised not to breastfeed their infants. HIV Infection Among Infants and Children Diagnosis of HIV infection in a pregnant woman indicates the need to consider whether additional children are infected. Infants and young children with HIV infection differ from adults and adolescents with respect to the diagnosis, clinical presentation, and management of HIV disease. For example, because maternal HIV antibody passes through the placenta, antibody tests for HIV are expected to be positive in the sera of both infected and uninfected infants born to seropositive mothers. A definitive determination of HIV infection for an infant aged <18 months should be based on laboratory evidence of HIV in blood or tissues by culture, nucleic acid, or antigen detection. 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 (21,30). Diseases Characterized by Genital UlcersManagement of Patients Who Have Genital UlcersIn 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, genital herpes is the most prevalent of these diseases. More than one of these diseases sometimes is present in a patient who has genital ulcers. Each disease has been associated with an increased risk for HIV infection. Not all genital ulcers are caused by sexually transmitted infections. A diagnosis based only on the patient's medical history and physical examination often is inaccurate. Therefore, evaluation of all patients who have genital ulcers should include a serologic test for syphilis and a diagnostic evaluation for genital herpes; in settings where chancroid is prevalent, a test for Haemophilus ducreyi should also be performed. Specific tests for evaluation of genital ulcers include
No FDA-approved PCR test for these organisms is available in the United States, but such testing can be performed by commercial laboratories that have developed their own PCR tests. Type-specific serology for HSV type 2 may be helpful in identifying persons with genital herpes (see Genital Herpes). Biopsy of ulcers may be helpful in identifying the cause of unusual ulcers or ulcers that do not respond to initial therapy. HIV testing should be performed in the management of patients who have genital ulcers caused by T. pallidum or H. ducreyi. Such testing should be considered for those who have ulcers caused by HSV (see sections on Syphilis, Chancroid, and Genital Herpes). Health-care providers often must treat patients before test results are available because early treatment decreases the possibility of ongoing transmission and because successful treatment of genital herpes depends upon prompt initiation of therapy. In this circumstance, the clinician should treat for the diagnosis considered most likely on the basis of clinical presentation and epidemiologic circumstances. Sometimes treatment must be initiated for additional conditions because of diagnostic uncertainty. Even after complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no laboratory-confirmed diagnosis. ChancroidIn the United States, chancroid usually occurs in discrete outbreaks, although the disease is endemic in some areas. Chancroid is a cofactor for HIV transmission; high rates of HIV infection among patients who have chancroid occur in the United States and other countries. About 10% of persons who have chancroid acquired in the United States are coinfected with T. pallidum or HSV; this percentage is higher in persons acquiring chancroid outside the United States. A definitive diagnosis of chancroid requires identification of H. ducreyi on special culture media that is not widely available from commercial sources; even using these media, sensitivity is <80%. No FDA-approved PCR test for H. ducreyi is available in the United States, but such testing can be performed by commercial laboratories that have developed their own PCR test. A probable diagnosis, for both clinical and surveillance purposes, can be made if all 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; c) the clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid; and d) a test for HSV performed on the ulcer exudate is negative. The combination of a painful ulcer and tender inguinal adenopathy, symptoms occurring in one third of patients, suggests a diagnosis of chancroid; when accompanied by suppurative inguinal adenopathy, these signs are almost pathognomonic. Treatment Successful treatment for chancroid cures the infection, resolves the clinical symptoms, and prevents transmission to others. In advanced cases, scarring can result despite successful therapy.
NOTE: Ciprofloxacin is contraindicated for pregnant and lactating women. 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 patients with HIV infection do not respond as well to treatment as those who are circumcised or HIV-negative. Patients should be tested for HIV infection at the time chancroid is diagnosed. Patients should be retested for syphilis and HIV 3 months after the diagnosis of chancroid if the initial test results were negative. Follow-Up Patients should be re-examined 3--7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 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 used 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 >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 needle aspiration or incision and drainage, despite otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage may be preferred because of reduced 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 the patient's onset of symptoms. Special Considerations Pregnancy The safety and efficacy of azithromycin for pregnant and lactating women have not been established. Ciprofloxacin is contraindicated during pregnancy and lactation. No adverse effects of chancroid on pregnancy outcome have been reported. HIV Infection HIV-infected patients who have chancroid should be monitored closely because, as a group, these patients are more likely to experience treatment failure and to have ulcers that heal more slowly. HIV-infected patients may require longer courses of therapy than those recommended for HIV-negative patients, and treatment failures can 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 specialists suggest using the erythromycin 7-day regimen for treating HIV-infected persons. Genital Herpes Simplex Virus InfectionsGenital herpes is a recurrent, life-long viral infection. Two serotypes of HSV have been identified: HSV-1 and HSV-2. Most cases of recurrent genital herpes are caused by HSV-2. At least 50 million persons in the United States have genital HSV infection. Most persons infected with HSV-2 have not been diagnosed. Many such persons have mild or unrecognized infections but shed virus intermittently in the genital tract. Most genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs. Rarely, first-episode genital herpes is manifested by severe disease that may require hospitalization. Diagnosis of HSV Infection The clinical diagnosis of genital herpes is both insensitive and nonspecific. The typical painful multiple vesicular or ulcerative lesions are absent in many infected persons. Up to 30% of first-episode cases of genital herpes are caused by HSV-1, but recurrences are much less frequent for genital HSV-1 infection than genital HSV-2 infection. Therefore, the distinction between HSV serotypes influences prognosis and counseling. For these reasons, the clinical diagnosis of genital herpes should be confirmed by laboratory testing. Both virologic tests and type-specific serologic tests for HSV should be available in clinical settings that provide care for patients with STDs or those at risk for STDs. Virologic Tests Isolation of HSV in cell culture is the preferred virologic test in patients who present with genital ulcers or other mucocutaneous lesions. The sensitivity of culture declines rapidly as lesions begin to heal, usually within a few days of onset. Some HSV antigen detection tests, unlike culture and the direct fluorescent antibody test, do not distinguish HSV-1 from HSV-2. Polymerase chain reaction (PCR) assays for HSV DNA are highly sensitive, but their role in the diagnosis of genital ulcer disease has not been well-defined. However, PCR is available in some laboratories and is the test of choice for detecting HSV in spinal fluid for diagnosis of HSV-infection of the central nervous system (CNS). Cytologic detection of cellular changes of herpes virus infection is insensitive and nonspecific, both in genital lesions (Tzanck preparation) and cervical Pap smears, and should not be relied on for diagnosis of HSV infection. Type-specific Serologic Tests Both type-specific and nonspecific antibodies to HSV develop during the first several weeks following infection and persist indefinitely. Because almost all HSV-2 infections are sexually acquired, type-specific HSV-2 antibody indicates anogenital infection, but the presence of HSV-1 antibody does not distinguish anogenital from orolabial infection. Accurate type-specific assays for HSV antibodies must be based on the HSV-specific glycoprotein G2 for the diagnosis of infection with HSV-2 and glycoprotein G1 for diagnosis of infection with HSV-1. Such assays first became commercially available in 1999, but older assays that do not accurately distinguish HSV-1 from HSV-2 antibody, despite claims to the contrary, remain on the market. Therefore, the serologic type-specific gG-based assays should be specifically requested when serology is performed. Currently, the FDA-approved, gG-based type-specific assays include POCkit™HSV-2 (manufactured by Diagnology); HerpeSelect™-1 ELISA IgG or HerpeSelect™-2 ELISA IgG (manufactured by Focus Technology, Inc.); and HerpeSelect™ 1 and 2 Immunoblot IgG (manufactured by Focus Technology, Inc.). The POCkit™-HSV-2 assay is a point-of-care test that provides results for HSV-2 antibodies from capillary blood or serum during a clinic visit. The Focus Technology assays are laboratory-based. The sensitivities of these tests for detection of HSV-2 antibody vary from 80% to 98%, and false-negative results may occur, especially at early stages of infection. The specificities of these assays are >96%. False-positive results can occur, especially in patients with low likelihood of HSV infection. Therefore, repeat testing or a confirmatory test (e.g., an immunoblot assay if the initial test was an ELISA) may be indicated in some settings. Because false-negative HSV cultures are common, especially in patients with recurrent infection or with healing lesions, type-specific serologic tests are useful in confirming a clinical diagnosis of genital herpes. Additionally, such tests can be used to diagnose persons with unrecognized infection and to manage sex partners of persons with genital herpes. Although serologic assays for HSV-2 should be available for persons who request them, screening for HSV-1 or HSV-2 infection in the general population is not indicated. Principles of Management of Genital Herpes Antiviral chemotherapy offers clinical benefits to most symptomatic patients and is the mainstay of management. In addition, counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management. Systemic antiviral drugs partially control the symptoms and signs of herpes episodes when used to treat first clinical episodes and recurrent episodes or when used as daily suppressive therapy. However, these drugs neither eradicate latent virus nor affect the risk, frequency, or severity of recurrences after the drug is discontinued. Randomized trials indicate that three antiviral medications provide clinical benefit for genital herpes: acyclovir, valacyclovir, and famciclovir (31--41). Valacyclovir is the valine ester of acyclovir and has enhanced absorption after oral administration. Famciclovir, a pro-drug of penciclovir, also has high oral bioavailability. Topical therapy with antiviral drugs offers minimal clinical benefit, and its use is not recommended. First Clinical Episode of Genital Herpes Many patients with first-episode herpes present with mild clinical manifestations but later develop severe or prolonged symptoms. Therefore, most patients with initial genital herpes should receive antiviral therapy.
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. However, no comparative studies have been conducted, and whether these forms of HSV infection require higher doses of antiviral drugs than used for genital herpes is unknown. Valacyclovir and famciclovir probably are also effective for acute HSV proctitis or oral infection, but clinical experience is lacking. Recurrent Episodes of HSV Disease Most patients with symptomatic, first-episode genital HSV-2 infection subsequently experience recurrent episodes of genital lesions; recurrences are much less frequent following initial genital HSV-1 infection. Antiviral therapy for recurrent genital herpes can be administered either episodically, to ameliorate or shorten the duration of lesions, or continuously as suppressive therapy to reduce the frequency of recurrences. Many patients, including those with mild or infrequent recurrent outbreaks, benefit from antiviral therapy; therefore, options for treatment should be discussed with all patients. Episodic Therapy for Recurrent Genital Herpes Effective episodic treatment of recurrent herpes requires initiation of therapy within 1 day of lesion onset, or during the prodrome that precedes some outbreaks. The patient should be provided with a supply of drug or a prescription for the medication with instructions to self-initiate treatment immediately when symptoms begin.
For episodic therapy, a randomized controlled trial indicated that a 3-day course of valacyclovir 500 mg twice daily is as effective as a 5-day course. Similar studies have not been done with acyclovir and famciclovir. Suppressive Therapy for Recurrent Genital Herpes Suppressive therapy reduces the frequency of genital herpes recurrences by 70%--80% among patients who have frequent recurrences (i.e., >6 recurrences per year), and many patients report no symptomatic outbreaks. Treatment probably is also effective in patients with less frequent recurrences, although definitive data are lacking. Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as 6 years, and with valacyclovir or famciclovir for 1 year. Quality of life often is improved in patients with frequent recurrences who receive suppressive compared with episodic treatment. The frequency of recurrent outbreaks diminishes over time in many patients, and the patient's psychological adjustment to the disease may change. Therefore, periodically during suppressive treatment (e.g., once a year), discontinuation of therapy should be discussed with the patient to reassess the need for continued therapy. Suppressive antiviral therapy reduces but does not eliminate subclinical viral shedding. Therefore, the extent to which suppressive therapy prevents HSV transmission is unknown.
Valacyclovir 500 mg once a day might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (i.e., >10 episodes per year). Few comparative studies of valacyclovir or famciclovir with acyclovir have been conducted. The results of these studies suggest that valacyclovir and famciclovir are comparable to acyclovir in clinical outcome (35--39). Ease of administration and cost also are important considerations for prolonged treatment. Severe Disease IV acyclovir therapy should be provided for patients who have severe disease or complications that necessitate hospitalization, such as disseminated infection, pneumonitis, hepatitis, or complications of the central nervous system (e.g., meningitis or encephalitis). The recommended regimen is acyclovir 5--10 mg/kg body weight IV every 8 hours for 2--7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days total therapy. Counseling Counseling of infected persons and their sex partners is critical to management of genital herpes. Counseling has two main goals: to help patients cope with the infection and to prevent sexual and perinatal transmission. 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. Numerous resources, including the CDC National STD/HIV Hotline (tel: 800-227-8922), web sites (http://www.ashastd.org), and printed materials are available to assist patients and clinicians in counseling. HSV-infected persons may express anxiety about genital herpes that does not reflect the actual clinical severity of their disease; the psychological impact of infection often is substantial. Common concerns about genital herpes include the severity of initial clinical manifestations, recurrent episodes, sexual relationships and transmission to sex partners, and ability to bear healthy children. The misconception that HSV causes cancer should be dispelled, because the role of HSV-2 in cervical cancer is at most that of a cofactor, not a primary etiologic agent. Specific counseling messages should include the following information.
Management of Sex Partners The sex partners of patients who have genital herpes likely benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions. Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions, educated to recognize symptoms of herpes, and offered type-specific serologic testing for HSV infection. Special Considerations Allergy, Intolerance, and Adverse Reactions Allergic and other adverse reactions to acyclovir, valacyclovir, and famciclovir are rare. Desensitization to acyclovir has been described (42). HIV Infection Immunocompromised patients may have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and may be severe, painful, and atypical. Episodic or suppressive therapy with oral antiviral agents is often beneficial.
In the doses recommended for treatment of genital herpes, acyclovir, valacyclovir, and famciclovir are safe for use in immunocompromised patients. For severe cases, initiating therapy with acyclovir 5--10 mg/kg body weight IV every 8 hours may be necessary. If lesions persist or recur in a patient receiving antiviral treatment, HSV resistance should be suspected and a viral isolate obtained for sensitivity testing. Such patients should be managed in consultation with a specialist, and 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. This preparation is not commercially available and must be compounded at a pharmacy. Genital Herpes in Pregnancy 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 (30%--50%) among women who acquire genital herpes near the time of delivery and is low (<1%) among women with histories of recurrent herpes at term or who acquire genital HSV during the first half of pregnancy. However, because recurrent genital herpes is much more common than initial HSV infection during pregnancy, the proportion of neonatal HSV infections acquired from mothers with recurrent herpes remains high. Prevention of neonatal herpes depends both on preventing acquisition of genital HSV infection during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery. Women without known genital herpes should be counseled to avoid intercourse during the third trimester with partners known or suspected of having genital herpes. In addition, pregnant women without known orolabial herpes should be advised to avoid cunnilingus during the third trimester with partners known or suspected to have orolabial herpes. Some specialists believe type-specific serologic tests are useful to identify pregnant women at risk for HSV infection and to guide counseling with regard to the risk of acquiring genital herpes during pregnancy. Such testing and counseling may be especially important when a woman's sex partner has HSV infection. All pregnant women should be asked whether they have a history of genital herpes. At the onset of labor, all women should be questioned carefully about symptoms of genital herpes, including prodrome, and all women should be examined carefully for herpetic lesions. Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally. Most specialists recommend that women with recurrent genital herpetic lesions at the onset of labor deliver by cesarean section to prevent neonatal herpes. However, abdominal delivery does not completely eliminate the risk for HSV transmission to the infant. The results of viral cultures during pregnancy in women with or without visible herpetic lesions do not predict viral shedding at the time of delivery, and therefore routine viral cultures of pregnant women with recurrent genital herpes are not recommended. The safety of systemic acyclovir, valacyclovir, and famciclovir therapy in pregnant women has not been established. Available data do not indicate an increased risk for major birth defects compared with the general population in women treated with acyclovir during the first trimester (43). These findings provide some assurance to women who have had prenatal exposure to acyclovir. However, available data are insufficient to reach definitive conclusions regarding the risks to the newborn associated with acyclovir treatment during pregnancy. The experience with prenatal exposure to valacyclovir and famciclovir is too limited to provide useful information on pregnancy outcomes. Acyclovir may be administered orally to pregnant women with first episode genital herpes or severe recurrent herpes and should be administered IV to pregnant women with severe HSV infection. Preliminary data suggest that acyclovir treatment late in pregnancy might reduce the frequency of cesarean sections among women who have recurrent genital herpes by diminishing the frequency of recurrences at term (44,45), and some specialists recommend such treatment. The risk for herpes is high in infants of women who acquire genital HSV in late pregnancy; such women should be managed in consultation with an HSV specialist. Some specialists recommend acyclovir therapy in this circumstance, some recommend routine cesarean section to reduce the risk for neonatal herpes, and others recommend both. Neonatal Herpes Infants exposed to HSV during birth, as documented by virologic testing or presumed by observation of lesions, should be followed carefully in consultation with a specialist. Some specialists recommend that such infants undergo surveillance cultures of mucosal surfaces to detect HSV infection before development of clinical signs of neonatal herpes. Some specialists recommend the use of acyclovir for infants born to women who acquired HSV near term, because the risk for neonatal herpes is high for these infants. All infants who have evidence of neonatal herpes should be promptly evaluated and treated with systemic acyclovir. The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease, or 14 days for disease limited to the skin and mucous membranes. Granuloma Inguinale (Donovanosis)Granuloma inguinale is a genital ulcerative disease caused by the intracellular Gram-negative bacterium Calymmatobacterium granulomatis. The disease occurs rarely in the United States, although it is endemic in certain tropical and developing areas, including India; Papua, New Guinea; central Australia; and southern Africa. Clinically, the disease commonly presents as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular ("beefy red appearance") and bleed easily on contact. However, the clinical presentation can also include hypertrophic, necrotic, or sclerotic variants. The causative organism is difficult to culture, and diagnosis requires visualization of dark-staining Donovan bodies on tissue crush preparation or biopsy. The lesions may develop secondary bacterial infection or may be coinfected with another sexually transmitted pathogen. Treatment Treatment halts progression of lesions, although prolonged therapy may be required to permit granulation and reepithelialization of the ulcers. Relapse can occur 6--18 months after apparently effective therapy. Several antimicrobial regimens have been effective, but few controlled trials have been published.
Therapy should be continued at least 3 weeks or until all lesions have completely healed. Some specialists recommend addition of an aminoglycoside (e.g., gentamicin 1 mg/kg IV every 8 hours) to the above regimens if improvement is not evident within the first few days of therapy. Follow-Up Patients should be followed clinically until signs and symptoms have resolved. Management of Sex Partners Persons who have had sexual contact with a patient who has granuloma inguinale within the 60 days before onset of the patient's symptoms should be examined and offered therapy. However, the value of empiric therapy in the absence of clinical signs and symptoms has not been established. Special Considerations Pregnancy Pregnancy is a relative contraindication to the use of sulfonamides. Pregnant and lactating women should be treated with the erythromycin regimen, and consideration should be given to the addition of a parenteral aminoglycoside (e.g., gentamicin). Azithromycin may prove useful for treating granuloma inguinale in pregnancy, but published data are lacking. Doxycycline and ciprofloxacin are contraindicated in pregnant women. HIV Infection Persons with both granuloma inguinale and HIV infection should receive the same regimens as those who are HIV negative. Consideration should be given to the addition of a parenteral aminoglycoside (e.g., gentamicin). Lymphogranuloma VenereumLymphogranuloma venereum (LGV) is caused by C. trachomatis serovars L1, L2, or L3. The disease occurs rarely in the United States. The most common clinical manifestation of LGV among heterosexuals is tender inguinal and/or femoral lymphadenopathy that is most commonly unilateral. Women and homosexually active men may have proctocolitis or inflammatory involvement of perirectal or perianal lymphatic tissues resulting in fistulas and strictures. A self-limited genital ulcer sometimes occurs at the site of inoculation. However, by the time patients seek care, the ulcer usually has disappeared. The diagnosis of LGV is usually made serologically and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers. Complement fixation titers >1:64 are consistent with the diagnosis of LGV. The diagnostic utility of serologic methods other than complement fixation is unknown. 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.
Some STD specialists believe azithromycin 1.0 g orally once weekly for 3 weeks is likely effective, although clinical data are lacking. Follow-Up Patients should be followed clinically until signs and symptoms have resolved. Management of Sex Partners Persons who have had sexual contact with a patient who has LGV within the 30 days before onset of the patient's symptoms should be examined, tested for urethral or cervical chlamydial infection, and treated. Special Considerations Pregnancy Pregnant and lactating women should be treated with erythromycin. Azithromycin may prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women. HIV Infection Persons with both LGV and HIV infection should receive the same regimens as those who are HIV-negative. Prolonged therapy may be required, and delay in resolution of symptoms may occur. SyphilisGeneral 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 but are not limited to skin rash, mucocutaneous lesions, and lymphadenopathy), or tertiary infection (e.g., cardiac, ophthalmic, auditory abnormalities, and gummatous lesions). Latent infections (i.e., those lacking clinical manifestations) are detected by serologic testing. Latent syphilis acquired within the preceding year is referred to as early latent syphilis; all other cases of latent syphilis are either late latent syphilis or latent syphilis of unknown duration. Treatment for both late latent syphilis and tertiary syphilis theoretically may require a longer duration of therapy because organisms are dividing more slowly; however, the validity of this concept has not been assessed. Diagnostic Considerations and Use of Serologic Tests Darkfield examinations and direct fluorescent antibody 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 tests (e.g., Venereal Disease Research Laboratory [VDRL] and Rapid Plasma Reagin [RPR]) and b) treponemal tests (e.g., fluorescent treponemal antibody absorbed [FTA-ABS] and T. pallidum particle agglutination [TP-PA]). The use of only one type of serologic test is insufficient for diagnosis, because false-positive nontreponemal test results may 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), is considered necessary to demonstrate a clinically significant difference between two nontreponemal test results that were obtained using the same serologic test. Sequential serologic tests in individual patients should be performed by using the same testing method (e.g., VDRL or RPR), preferably by the same laboratory. The VDRL and RPR are equally valid assays, but quantitative results from the two tests cannot be compared directly because RPR titers often are slightly higher than VDRL titers. Nontreponemal tests usually become nonreactive with time after treatment; however, in some patients, nontreponemal antibodies can persist at a low titer for a long period of time, sometimes for the life of the patient. This response is referred to as the "serofast reaction." 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 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. Some HIV-infected patients can have atypical serologic test results (i.e., unusually high, unusually low, or fluctuating titers). For such patients, when serologic tests and clinical syndromes suggestive of early syphilis do not correspond with one another, use of other tests (e.g., biopsy and direct microscopy) should be considered. However, for most HIV-infected patients, serologic tests are accurate and reliable for the diagnosis of syphilis and for following the response to treatment. No test can be used alone to diagnose neurosyphilis. The VDRL-CSF is highly specific, but it is insensitive. Most other tests are both insensitive and nonspecific and must be interpreted in relation to other test results and the clinical assessment. Therefore, the diagnosis of neurosyphilis usually depends 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 (>5 WBCs/mm3) in patients with neurosyphilis; this count also is a sensitive measure of the effectiveness of therapy. The VDRL-CSF is the standard serologic test for CSF, and 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 specialists 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, but the test is highly sensitive. Therefore, some specialists believe that a negative CSF FTA-ABS test excludes neurosyphilis. Treatment Penicillin G, administered parenterally, 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. However, neither combinations of benzathine penicillin and procaine penicillin nor oral penicillin preparations are considered appropriate for the treatment of syphilis. 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 the opinions of persons knowledgeable about STDs and are reinforced by case series, clinical trials, and 50 years of clinical experience. Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin. Skin testing for penicillin allergy may be useful in pregnant women; such testing also is useful in other patients (see Management of Patients Who Have a History of Penicillin Allergy). The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occurs within the first 24 hours after any therapy for syphilis. Patients should be informed about this possible adverse reaction. The Jarisch-Herxheimer reaction occurs most often among patients who have early syphilis. Antipyretics may be used, but they have not been proven to prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress in pregnant women. This concern should not prevent or delay therapy (see Syphilis During Pregnancy). 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.
For identification of at-risk partners, the time periods before treatment 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 Parenteral penicillin G has been used effectively for more than 50 years to achieve clinical resolution (i.e., healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for nonpenicillin regimens.
NOTE: Recommendations for treating pregnant women and HIV-infected patients for syphilis are discussed in separate sections.
After the newborn period, children with syphilis should have a CSF examination to detect asymptomatic neurosyphilis, and birth and maternal medical records should be reviewed to assess whether such children have congenital or acquired syphilis (see Congenital Syphilis). Children with acquired primary or secondary syphilis should be evaluated (e.g., through consultation with child-protection services) (see Sexual Assault or Abuse of Children) and treated by using the following pediatric regimen.
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. Patients who have syphilis and who also have symptoms or signs suggesting neurologic disease (e.g., meningitis) or ophthalmic disease (e.g., uveitis) should have an evaluation that includes CSF analysis and ocular slit-lamp examination. Treatment should be guided by 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 limited number of patients after treatment with the penicillin regimens recommended for primary and secondary syphilis. Therefore, unless clinical signs or symptoms of neurologic or ophthalmic involvement are present, CSF analysis is not recommended for routine evaluation of patients who have primary or secondary syphilis. Follow-Up Treatment failure can occur with any regimen. However, assessing response to treatment often is difficult, and definitive criteria for cure or failure have not been established. Nontreponemal test titers may decline more slowly for patients who previously had syphilis. Patients should be reexamined clinically and serologically 6 months and 12 months following treatment; 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., compared with the maximum or baseline titer at the time of treatment) probably failed treatment or were reinfected. These patients should be re-treated and reevaluated for HIV infection. Because treatment failure usually cannot be reliably distinguished from reinfection with T. pallidum, a CSF analysis also should be performed. A recent clinical trial demonstrated that 15% of patients with early syphilis treated with the recommended therapy will not achieve a two dilution decline in nontreponemal titer used to define response at 1 year following treatment. Failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis is indicative of probable treatment failure. Persons for whom titers remain serofast 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. Because treatment failure may be the result of unrecognized CNS infection, some specialists recommend CSF examination in such situations. When patients are re-treated, most STD specialists recommend administering weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks, unless CSF examination indicates that neurosyphilis is present. In rare instances, serologic titers do not decline despite a negative CSF examination and a repeated course of therapy. Additional therapy or repeated CSF examinations are not warranted in these circumstances. Management of Sex Partners See General Principles, Management of Sex Partners. Special Considerations Penicillin Allergy. Data to support the use of alternatives to penicillin in the treatment of early syphilis are limited. However, several therapies might be considered effective in nonpregnant, penicillin-allergic patients who have primary or secondary syphilis. Doxycycline (100 mg orally twice daily for 14 days) and tetracycline (500 mg four times daily for 14 days) are regimens that have been used for many years. Compliance is likely to be better with doxycycline than tetracycline, because tetracycline can cause gastrointestinal side effects. Although limited clinical studies, along with biologic and pharmacologic evidence, suggest that ceftriaxone is effective for treating early syphilis, the optimal dose and duration of ceftriaxone therapy have not been defined. However, some specialists recommend 1 gram daily either IM or IV for 8--10 days. Preliminary data suggest that azithromycin may be effective as a single oral dose of 2 grams. Because the efficacy of these therapies is not well documented, close follow-up of persons receiving these therapies is essential. The use of any of these therapies in HIV-infected persons has not been studied; the use of doxycycline, ceftriaxone, and azithromycin among such persons must be undertaken with caution. Patients with penicillin allergy whose compliance with therapy or follow-up cannot be ensured should be desensitized and treated with benzathine penicillin. Skin testing for penicillin allergy may be useful in some circumstances in which the reagents and expertise are available to perform the test adequately (see Management of Patients Who Have a History of Penicillin Allergy). 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. See Syphilis Among HIV-Infected Persons. Latent syphilis is defined as syphilis characterized by seroreactivity without 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 diagnosed 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 documented to have primary, secondary, or early latent syphilis. Patients who have latent syphilis of unknown duration should be managed as if they have 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. All patients with latent syphilis should have careful examination of all accessible mucosal surfaces (i.e., the oral cavity, the perineum in women, and underneath the foreskin in uncircumcised men) to evaluate for internal mucosal lesions. All patients who have syphilis should be tested for HIV infection. Treatment of latent syphilis usually does not affect transmission and 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. The following regimens are recommended for nonallergic patients who have normal CSF examinations (if performed).
After the newborn period, children with syphilis should have a CSF examination to exclude neurosyphilis. In addition, birth and maternal medical records should be reviewed to assess whether children have 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 who have normal CSF examination results.
Other Management Considerations All patients who have latent syphilis should be evaluated clinically for evidence of tertiary disease (e.g., aortitis, 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. Some specialists recommend performing a CSF examination on all patients who have latent syphilis and a nontreponemal serologic test of >1:32. The risk of neurosyphilis in this circumstance is unknown. If a CSF examination is performed and the results indicate abnormalities consistent with neurosyphilis, the patient should be treated for neurosyphilis (see Neurosyphilis). If a patient misses a dose of penicillin in the course of weekly therapy for late syphilis, the appropriate course of action is unclear. Pharmacologic considerations suggest that an interval of 10--14 days between doses of benzathine penicillin for late syphilis or latent syphilis of unknown duration might be acceptable before restarting the sequence of injections. Missed doses should not be considered acceptable for pregnant patients receiving therapy for late latent syphilis; pregnant women who miss any dose of therapy must repeat the full course of therapy. Follow-Up. Quantitative nontreponemal serologic tests should be repeated at 6, 12, and 24 months. Patients with a normal CSF examination should be re-treated for latent syphilis if a) titers increase fourfold, b) an initially high titer (>1:32) fails to decline at least fourfold (i.e., two dilutions) within 12--24 months of therapy, or c) signs or symptoms attributable to syphilis develop. In rare instances, despite a negative CSF examination and a repeated course of therapy, serologic titers may still not decline. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear. Management of Sex Partners. See General Principles, Management of Sex Partners. Special Considerations Penicillin Allergy. The effectiveness of alternatives to penicillin in the treatment of latent syphilis has not been well documented. Nonpregnant patients allergic to penicillin who have clearly defined early latent syphilis should respond to therapies recommended as alternatives to penicillin for the treatment of primary and secondary syphilis (see Treatment of Primary and Secondary Syphilis). The only acceptable alternatives for the treatment of late latent syphilis or latent syphilis of unknown duration are doxycycline (100 mg orally twice daily) or tetracycline (500 mg orally four times daily) both for 28 days. These therapies should be used only in conjunction with close serologic and clinical follow-up. The efficacy of these alternative regimens in HIV-infected persons has not been studied, and thus must be considered with caution. 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. See Syphilis Among HIV-Infected Persons. Tertiary Syphilis Tertiary syphilis refers to gumma and cardiovascular syphilis, but not to all neurosyphilis. Patients who are not allergic to penicillin and have no evidence of neurosyphilis should be treated with the following regimen.
Other Management Considerations Patients who have symptomatic late syphilis should be given a CSF examination before therapy is initiated. Some providers 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 infectious diseases specialist. Follow-Up. Limited information is available concerning clinical response and follow-up of patients who have tertiary syphilis. Management of Sex Partners. See General Principles, Management of Sex Partners. Special Considerations Penicillin Allergy. Patients allergic to penicillin should be treated according to treatment regimens recommended 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. See Syphilis Among HIV-Infected Persons. Treatment CNS disease can occur during any stage of syphilis. A patient who has clinical evidence of neurologic involvement with syphilis (e.g., cognitive dysfunction, motor or sensory deficits, 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 patients with 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, and optic neuritis) should be treated with the following regimen.
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