Sexually Transmitted Diseases (STDs)

Vaccine-Preventable STDs

Several STDs can be effectively prevented through pre-exposure vaccination with widely available vaccines, including HAV, HBV, and HPV. Vaccines for other STDs (e.g., HIV and HSV) are under development or are undergoing clinical trials. This guidance focuses largely on integrating the use of available vaccines into STD prevention and treatment activities.

Every person being evaluated or treated for an STD should receive hepatitis B vaccination unless already vaccinated. In addition, some persons (e.g., MSM and IDUs) should receive hepatitis A vaccination.

Hepatitis A

Hepatitis A, caused by infection with HAV, has an incubation period of approximately 28 days (range: 15–50 days). HAV replicates in the liver and is shed in high concentrations in feces from 2 weeks before to 1 week after the onset of clinical illness. HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease (CLD). However, 10%–15% of patients experience a relapse of symptoms during the 6 months after acute illness. Acute liver failure from hepatitis A is rare (overall case-fatality rate: 0.5%). The risk for symptomatic infection is directly related to age, with >80% of adults having symptoms compatible with acute viral hepatitis and most children having either asymptomatic or unrecognized infection. Antibody produced in response to HAV infection persists for life and confers protection against reinfection.

HAV infection is primarily transmitted by the fecal-oral route, by either person-to-person contact or through consumption of contaminated food or water. Although viremia occurs early in infection and can persist for several weeks after onset of symptoms, bloodborne transmission of HAV is uncommon. HAV occasionally is detected in saliva in experimentally infected animals, but transmission by saliva has not been demonstrated.

In the United States, almost half of all persons with hepatitis A report having no risk factor for the disease. Among adults with identified risk factors, most cases occur among international travelers, household or sexual contacts, nonhousehold contacts (e.g., those encountered through play and daycare), and IDUs (437). Because transmission of HAV during sexual activity probably results from fecal-oral contact, measures typically used to prevent the transmission of other STDs (e.g., use of condoms) do not prevent HAV transmission. In addition, efforts to promote good personal hygiene have not been successful in interrupting outbreaks of hepatitis A. Vaccination is the most effective means of preventing HAV transmission among persons at risk for infection (e.g., MSM, illegal drug users, and persons with CLD), many of whom might seek services in STD clinics.

Diagnosis

The diagnosis of hepatitis A cannot be made on clinical grounds alone; serologic testing also is required. The presence of IgM antibody to HAV is diagnostic of acute HAV infection. A positive test for total anti-HAV indicates immunity to HAV infection but does not differentiate current from previous HAV infection. Although usually not sensitive enough to detect the low level of protective antibody after vaccination, anti-HAV tests also might be positive after hepatitis A vaccination.

Treatment

Patients with acute hepatitis A usually require only supportive care, with no restrictions in diet or activity. Hospitalization might be necessary for patients who become dehydrated because of nausea and vomiting and is critical for patients with signs or symptoms of acute liver failure. Medications that might cause liver damage or are metabolized by the liver should be used with caution among persons with hepatitis A.

Prevention

Two products are available for the prevention of HAV infection: hepatitis A vaccine (Table 2) and immune globulin (IG) for IM administration. Hepatitis A vaccines are prepared from formalin-inactivated, cell-culture–derived HAV and have been available in the United States since 1995, initially for persons aged ≥2 years. In 2005, the vaccines were approved by FDA for persons aged ≥12 months, and the vaccine is available for eligible children and adolescents aged <19 years through the VFC program (telephone: 800-232-4636).

TABLE 2. Recommended regimens: dose and schedule for hepatitis A vaccines

Vaccine	Age (yrs)	Dose	Volume (mL)	Two-dose schedule (months)*
HAVRIX†	1-18	720 (EL.U.)	0.5	0 (6–12)
	>18	1,440 (EL.U.)	1.0	0 (6–12)
VAQTA§	1-18	25 (U)	0.5	0 (6–18)
	>18	50 (U)	1.0	0 (6–18)

Source: CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(No. RR-7).
Abbreviations: EL.U = Enzyme-linked immunosorbent assay (ELISA) units; U = units.
* 0 months represents timing of the initial dose; subsequent numbers represent months after the initial dose.
† Hepatitis A vaccine, inactivated, GlaxoSmithKline Biologicals; this vaccine is also licensed for a 3-dose series in children aged 2–18 years, with 360 EL.U, 0.5 mL doses at 0, 1, and 6–12 months.
§ Hepatitis A vaccine, inactivated, Merck & Co., Inc.

Administered IM in a 2-dose series at 0 and 6–12 months, these vaccines induce protective antibody levels in virtually all adults. By 1 month after the first dose, 94%–100% of adults have protective antibody levels; 100% of adults develop protective antibody after a second dose. In randomized controlled trials, the equivalent of 1 dose of hepatitis A vaccine administered before exposure has been 94%–100% effective in preventing clinical hepatitis A (2). Kinetic models of antibody decline indicate that protective levels of antibody persist for at least 20 years.

IG is a sterile solution of concentrated immunoglobulins prepared from pooled human plasma processed by cold ethanol fractionation. In the United States, IG is produced only from plasma that has tested negative for hepatitis B surface antigen, antibodies to HIV and HCV, and HCV RNA. In addition, the process used to manufacture IG inactivates viruses (e.g., HBV, HCV, and HIV). When administered IM before or within 2 weeks after exposure to HAV, IG is >85% effective in preventing HAV infections.

A combined hepatitis A and hepatitis B vaccine has been developed and licensed for use as a 3-dose series in adults aged ≥18 years (Table 3). When administered IM on a 0-, 1-, and 6-month schedule, the vaccine has equivalent immunogenicity to that of the monovalent vaccines.

Pre-exposure Vaccination

Persons in the following groups who are likely to be treated in STD clinic settings should be offered hepatitis A vaccine: 1) all MSM; 2) illegal drug users (of both injection and noninjection drugs); and 3) persons with CLD, including persons with chronic HBV and HCV infection who have evidence of CLD.

Prevaccination Serologic Testing for Susceptibility

Approximately one third of the U.S. population has serologic evidence of previous HAV infection, which increases with age and reaches 75% among persons aged >70 years. Screening for HAV infection might be cost-effective in populations where the prevalence of infection is likely to be high (e.g., persons aged >40 years and persons born in areas of high HAV endemicity). The potential cost-savings of testing should be weighed against the cost and the likelihood that testing will interfere with initiating vaccination. Vaccination of a person who is already immune is not harmful.

Postvaccination Serologic Testing

Postvaccination serologic testing is not indicated because most persons respond to the vaccine. In addition, the commercially available serologic test is not sensitive enough to detect the low, but protective, levels of antibody produced by vaccination.

Postexposure Prophylaxis

Persons who recently have been exposed to HAV and who previously have not received hepatitis A vaccine should be administered a single dose of single-antigen vaccine or IG (0.02 mL/kg) as soon as possible. Information about the relative efficacy of vaccine compared with IG postexposure is limited, and no data are available for persons aged >40 years or those with underlying medical conditions. Therefore, decisions to use vaccine or IG should take into account patient characteristics associated with more severe manifestations of hepatitis A, including older age and CLD.

For healthy persons aged 12 months to 40 years, single-antigen hepatitis A vaccine at the age-appropriate dose is preferred over IG because of vaccine advantages, including long-term protection and ease of administration. For persons aged >40 years, IG is preferred because of the absence of information regarding vaccine performance and the more severe manifestations of hepatitis A in this age group; vaccine can be used if IG cannot be obtained. The magnitude of the risk for HAV transmission from the exposure should be considered in decisions to use IG or vaccine. IG should be used for children aged <12 months, immunocompromised persons, persons who have had diagnosed CLD, and persons for whom vaccine is contraindicated.

If IG is administered to persons for whom hepatitis A vaccine also is recommended, a dose of vaccine should be provided simultaneously with IG. The second vaccine dose should be administered according to the licensed schedule to complete the series. The efficacy of IG or vaccine when administered >2 weeks after exposure has not been established (438).

Special Considerations

Limited data indicate that vaccination of persons with CLD and of persons with advanced HIV infection results in lower seroprotection rates and antibody concentrations (4). In HIV-infected persons, antibody response might be directly related to CD4+ levels.

Hepatitis B

Hepatitis B is caused by infection with the hepatitis B virus (HBV). The incubation period from the time of exposure to onset of symptoms is 6 weeks to 6 months. The highest concentrations of HBV are found in blood, with lower concentrations found in other body fluids including wound exudates, semen, vaginal secretions, and saliva (439,440). HBV is more infectious and relatively more stable in the environment than other bloodborne pathogens like HCV and HIV.

HBV infection can be self-limited or chronic. In adults, only approximately half of newly acquired HBV infections are symptomatic, and approximately 1% of reported cases result in acute liver failure and death. Risk for chronic infection is inversely related to age at acquisition; approximately 90% of infected infants and 30% of infected children aged <5 years become chronically infected, compared with 2%–6% of persons who become infected as adults. Among persons with chronic HBV infection, the risk for premature death from cirrhosis or hepatocellular carcinoma (HCC) is 15%–25%.

HBV is efficiently transmitted by percutaneous or mucous membrane exposure to blood or body fluids that contain blood. The primary risk factors associated with infection among adolescents and adults are unprotected sex with an infected partner, unprotected sex with more than one partner, MSM, history of other STDs, and illegal injection-drug use. In addition, several studies have demonstrated the horizontal transmission of HBV, including through premastication, as a less common source of transmission (441,442).

CDC’s national strategy to eliminate transmission of HBV infection includes 1) prevention of perinatal infection through routine screening of all pregnant women for HBsAg and immunoprophylaxis of infants born to HBsAg-positive mothers or mothers whose HBsAg status is unknown, 2) routine infant vaccination, 3) vaccination of previously unvaccinated children and adolescents through age 18 years, and 4) vaccination of previously unvaccinated adults at increased risk for infection (3,4). High vaccination coverage rates, with subsequent declines in acute hepatitis B incidence, have been achieved among infants and adolescents (4,437,443). In contrast, vaccination coverage among most high-risk adult groups (e.g., persons with more than one sex partner in the previous 6 months, MSM, and IDUs) has remained low, and most new infections occur in these high-risk groups (3,108,444–446). STD clinics and other settings that provide services to high-risk adults are ideal sites in which to provide hepatitis B vaccination to adults at risk for HBV infection. All unvaccinated adults seeking services in these settings should be assumed to be at risk for hepatitis B and should be offered hepatitis B vaccination.

Diagnosis

Diagnosis of acute or chronic HBV infection requires serologic testing (Table 4). Because HBsAg is present in both acute and chronic infection, the presence of IgM antibody to hepatitis B core antigen (IgM anti-HBc) is diagnostic of acute or recently acquired HBV infection. Antibody to HBsAg (anti-HBs) is produced after a resolved infection and is the only HBV antibody marker present after vaccination. The presence of HBsAg and total anti-HBc, with a negative test for IgM anti-HBc, indicates chronic HBV infection. The presence of anti-HBc alone might indicate a false-positive result or acute, resolved, or chronic infection.

Treatment

No specific therapy is available for persons with acute hepatitis B; treatment is supportive. Persons with chronic HBV infection should be referred for evaluation to a physician experienced in the management of CLD. Therapeutic agents cleared by FDA for treatment of chronic hepatitis B can achieve sustained suppression of HBV replication and remission of liver disease in some persons. In addition, patients with chronic hepatitis B might benefit from screening to detect HCC at an early stage.

Prevention

Two products have been approved for hepatitis B prevention: hepatitis B immune globulin (HBIG) and hepatitis B vaccine (3,4). HBIG provides temporary (i.e., 3–6 months) protection from HBV infection and is typically used as PEP either as an adjunct to hepatitis B vaccination in previously unvaccinated persons or alone in persons who have not responded to vaccination. HBIG is prepared from plasma known to contain high concentrations of anti-HBs. The recommended dose of HBIG is 0.06 mL/kg.

Hepatitis B vaccine contains HBsAg produced in yeast by recombinant DNA technology and provides protection from HBV infection when used for both pre-exposure vaccination and PEP. The two available monovalent hepatitis B vaccines for use in adolescents and adults are Recombivax HB (Merck and Co., Inc., Whitehouse Station, New Jersey) and Engerix-B (GlaxoSmithKline Biologicals, Pittsburgh, Pennsylvania). A combination vaccine (hepatitis A and hepatitis B) for use in adults, Twinrix (GlaxoSmithKline Biologicals, Pittsburgh, Pennsylvania), also is available. The recommended HBV dose varies by product and age of recipient (Table 3).

When selecting a hepatitis B vaccination schedule, the health-care provider should consider the need to achieve completion of the vaccine series. Approved adolescent and adult schedules for both monovalent hepatitis B vaccine (i.e., Engerix-B and Recombivax HB) include the following: 0, 1, and 6 months; 0, 1, and 4 months; and 0, 2, and 4 months. A 4-dose schedule of Engerix-B at 0, 1, 2, and 12 months is licensed for all age groups. A 2-dose schedule of Recombivax HB adult formulation (10 µg) is licensed for adolescents aged 11–15 years. When scheduled to receive the second dose, adolescents aged >15 years should be switched to a 3-dose series, with doses two and three consisting of the pediatric formulation (5 µg) administered on an appropriate schedule. Twinrix can be administered to persons aged ≥18 years at risk for both HAV and HBV infections at 0, 1, and 6 months.

Hepatitis B vaccine should be administered IM in the deltoid muscle and can be administered simultaneously with other vaccines. For adolescents and adults, the needle length should be 1–2 inches, depending on the recipient’s weight (1 inch for females weighing <70 kg, 1.5 inches for males weighing <120 kg, and 2 inches for males and females weighing >120 kg and >100 kg, respectively). A 22- to 25-gauge needle is recommended. If the vaccine series is interrupted after the first or second dose of vaccine, the missed dose should be administered as soon as possible. The series does not need to be restarted after a missed dose.

In adolescents and healthy adults aged <40 years, approximately 30%–55% acquire a protective antibody response (anti-HBs ≥10 mIU/mL) after the first vaccine dose, 75% after the second, and >90% after the third. Vaccine-induced immune memory has been demonstrated to persist for at least 15–20 years. Periodic testing to determine antibody levels after routine vaccination in immunocompetent persons is not necessary, and booster doses of vaccine are not currently recommended.

Hepatitis B vaccination is generally well-tolerated by most recipients. Pain at the injection site and low-grade fever are reported by a minority of recipients. For children and adolescents, a causal association exists between receipt of hepatitis B vaccination and anaphylaxis: for each 1.1 million doses of vaccine administered, approximately one vaccinee will experience this type of reaction. No deaths have been reported in these patients (3,4,447). Vaccine is contraindicated in persons with a history of anaphylaxis after a previous dose of hepatitis B vaccine and in persons with a known anaphylactic reaction to any vaccine component. No evidence for a causal association has been demonstrated for other adverse events after administration of hepatitis B vaccine.

Pre-exposure Vaccination

Hepatitis B vaccination is recommended for all unvaccinated adolescents, all unvaccinated adults at risk for HBV infection, and all adults seeking protection from HBV infection. For adults, acknowledgement of a specific risk factor is not a requirement for vaccination.

Hepatitis B vaccine should be routinely offered to all unvaccinated persons attending STD clinics and to all unvaccinated persons seeking treatment for STDs in other settings. Other settings where all unvaccinated adults should be assumed to be at risk for hepatitis B and should receive hepatitis B vaccination include correctional facilities, facilities providing drug abuse treatment and prevention services, health-care settings serving MSM, and HIV testing and treatment facilities. All persons who receive clinical services in these settings should be offered hepatitis B vaccine unless they have a reliable vaccination history (i.e., a written, dated record of each dose of a complete series). In all settings, vaccination should be initiated even when completion of the vaccine series cannot be ensured.

Prevaccination Antibody Screening

Prevaccination serologic testing for susceptibility might be considered to reduce the cost of vaccinating adult populations that have an expected high prevalence (20%–30%) of HBV infection (e.g., IDUs and MSM, especially those in older age groups). In addition, prevaccination testing for susceptibility is recommended for unvaccinated household, sexual, and needle-sharing contacts of HBsAg-positive persons (108).

Anti-HBc is the test of choice for prevaccination testing; persons who are anti-HBc–positive should be tested for HBsAg. If persons are determined to be HBsAg negative, no further action is required. If persons are determined to be HBsAg positive, the person should be referred for medical follow-up to include counseling and evaluation for antiviral treatment (see Management of HBsAg-Positive Persons). In addition, all household members, sex partners, and needle-sharing partners of HBsAg-positive persons should be vaccinated.

Serologic testing should not be a barrier to vaccination of susceptible persons, especially in populations that are difficult to access. In most cases, the first vaccine dose should be administered immediately after collection of the blood sample for serologic testing. Vaccination of persons who are immune to HBV infection because of current or previous infection or vaccination does not increase the risk for adverse events.

Postvaccination Testing for Serologic Response

Serologic testing for immunity is not necessary after routine vaccination of adolescents or adults. However, such testing is recommended for persons whose subsequent clinical management depends on knowledge of their immune status (e.g., health-care workers or public safety workers at high risk for continued percutaneous or mucosal exposure to blood or body fluids). In addition, postvaccination testing is recommended for 1) HIV-infected persons and other immunocompromised persons to determine the need for revaccination and the type of follow-up testing and 2) sex and needle-sharing partners of HBsAg-positive persons to determine the need for revaccination and for other methods to protect themselves from HBV infection.

If indicated, testing should be performed 1–2 months after administration of the last dose of the vaccine series by using a method that allows determination of a protective level of anti-HBs (i.e., ≥10 mIU/mL). Persons determined to have anti-HBs levels of <10 mIU/mL after the primary vaccine series should be revaccinated with a 3-dose series and provided with anti-HBs testing 1–2 months after the third dose. Persons who do not respond to revaccination should be tested for HBsAg. If HBsAg positive, the person should receive appropriate management (see Management of HBsAg-Positive Persons); if HBsAg negative, the person should be considered susceptible to HBV infection and counseled concerning precautions to prevent HBV infection and the need for HBIG PEP for any known exposure (see Postexposure Prophylaxis).

Postexposure Prophylaxis

Both passive-active PEP (the administration of HBIG and hepatitis B vaccine at separate sites) and active PEP (the administration of hepatitis B vaccination alone) have been demonstrated to be highly effective in preventing transmission after exposure to HBV (4). HBIG alone also has been demonstrated to be effective in preventing HBV transmission, but with the availability of hepatitis B vaccine, HBIG typically is used as an adjunct to vaccination.

Exposure to HBsAg-Positive Source

Unvaccinated persons or persons known not to have responded to a complete hepatitis B vaccine series should receive both HBIG and hepatitis vaccine as soon as possible (preferably ≤24 hours) after a discrete, identifiable exposure to blood or body fluids that contain blood from an HBsAg-positive source (Table 5). Hepatitis B vaccine should be administered simultaneously with HBIG at a separate injection site, and the vaccine series should be completed by using the age-appropriate vaccine dose and schedule (Table 3). Exposed persons who are in the process of being vaccinated but who have not completed the vaccine series should receive the appropriate dose of HBIG (i.e., 0.06 mL/kg) and should complete the vaccine series. Exposed persons who are known to have responded to vaccination are considered protected; therefore, they need no additional doses of vaccine. Persons who have written documentation of a complete hepatitis B vaccine series who did not receive postvaccination testing should receive a single vaccine booster dose. Alternatively, these persons can be managed according to guidelines for management of persons with occupational exposure to blood or body fluids that contain blood (446).

Exposure to Source with Unknown HBsAg Status

Unvaccinated persons who have a discrete, identifiable exposure to blood or body fluids containing blood from a source with unknown HBsAg status should receive the hepatitis B vaccine series, with the first dose initiated as soon as possible after exposure (preferably within 24 hours) and the series completed by using the age-appropriate dose and schedule. Exposed persons who are not fully vaccinated should complete the vaccine series. Exposed persons with written documentation of a complete hepatitis B vaccine series require no further treatment.

Special Considerations

Pregnancy

All pregnant women receiving STD services should be tested for HBsAg, regardless of whether they have been previously tested or vaccinated. All HBsAg-positive pregnant women should be reported to state and local perinatal hepatitis B prevention programs. HBsAg-negative pregnant women seeking STD treatment who have not been previously vaccinated should receive hepatitis B vaccination. Additional information regarding management of HBsAg-positive pregnant women and their infants is available at http://www.cdc.gov/mmwr/PDF/rr/rr5416.pdf.

HIV Infection

HIV infection can impair the response to hepatitis B vaccination. HIV-infected persons should be tested for anti-HBs 1–2 months after the third vaccine dose (see Postvaccination Testing for Serologic Response). Modified dosing regimens, including a doubling of the standard antigen dose and administration of additional doses, might increase the response rate (130).

Management of HBsAg-Positive Persons

This section provides recommendations for management of all HBsAg-positive persons. Additional recommendations for management of HBsAg-positive persons who are coinfected with HIV are available (130).

• All persons with HBsAg-positive laboratory results should be reported to the state or local health department.
• To verify the presence of chronic HBV infection, HBsAg-positive persons should be retested. The absence of IgM anti-HBc or the persistence of HBsAg for 6 months indicates chronic HBV infection.
• Persons with chronic HBV infection should be referred for evaluation to a physician experienced in the management of CLD. Some patients with chronic hepatitis B will benefit from early intervention with antiviral treatment or screening to detect HCC at an early stage.
• Household, sexual, and needle-sharing contacts of chronically infected persons should be identified. Unvaccinated sex partners and household and needle-sharing contacts should be tested for susceptibility to HBV infection (see Prevaccination Antibody Screening) and should receive the first dose of hepatitis B vaccine immediately after collection of the blood sample for serologic testing. Susceptible persons should complete the vaccine series by using an age-appropriate vaccine dose and schedule.
• Sex partners of HBsAg-positive persons should be counseled to use latex condoms (448) to protect themselves from sexual exposure to infectious body fluids (e.g., semen and vaginal secretions), unless they have been demonstrated to be immune after vaccination (anti-HBs ≥ 10 mIU/mL) or previously infected (anti-HBc positive).
• To prevent or reduce the risk for transmission to others, HBsAg-positive persons should be advised about the risk for transmission to household, sexual, and needle-sharing contacts and the need for such contacts to receive hepatitis B vaccination. HBsAg-positive persons also should be advised to:
  • use methods (e.g., condoms) to protect nonimmune sex partners from acquiring HBV infection from sexual activity until the partner can be vaccinated and immunity documented;
  • cover cuts and skin lesions to prevent spread by infectious secretions or blood; – refrain from donating blood, plasma, body organs, other tissue, or semen; and
  • refrain from sharing household articles (e.g., toothbrushes, razors, or personal injection equipment) that could become contaminated with blood. In addition, HBsAg-positive persons should refrain from premasticating food provided to susceptible persons.
• To protect the liver from further harm, HBsAg-positive persons should be advised to:
  • avoid or limit alcohol consumption because of the effects of alcohol on the liver;
  • refrain from starting any new medicines, including OTC and herbal medicines, without checking with their health-care provider; and
  • obtain vaccination against hepatitis A if liver disease is determined to be present.

When seeking medical or dental care, HBsAg-positive persons should be advised to inform their health-care providers of their HBsAg status so that they can be appropriately evaluated and managed. The following counseling messages should be considered for HBsAg-positive persons:

• HBV is not usually spread by hugging, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact.
• Persons should not be excluded from work, school, play, child care, or other settings because they are infected with HBV.
• Involvement with a support group might help patients cope with chronic HBV infection.