Description

Hepatitis B is caused by the hepatitis B virus (HBV). The clinical manifestations of HBV infection range in severity from no symptoms to fulminant hepatitis. Signs and symptoms of hepatitis B may include fever, malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice (1).

Occurrence

HBV is transmitted through activities that involve contact with blood or blood-derived fluids. Such activities can include unprotected sex with an HBV-infected partner; shared needles used for injection of illegal drugs; work in health-care fields (medical, dental, laboratory, or other) that entails direct exposure to human blood; receiving blood transfusions that have not been screened for HBV; or having dental, medical, or cosmetic (e.g., tattooing or body piercing) procedures with needles or other equipment that are contaminated with HBV. In addition, open skin lesions, such as those due to impetigo, scabies, or scratched insect bites, can play a role in HBV transmission if direct exposure to wound exudates from HBV-infected persons occurs (1,2).

The prevalence of chronic HBV infection is low (<2%) in the general population in Northern and Western Europe, North America, Australia, New Zealand, Mexico, and Southern South America (Map 4-4). In the United States and many other developed countries, children and adolescents are routinely vaccinated against hepatitis B. The highest incidence of dis-ease is in younger adults, and most HBV infections are acquired through unprotected sex with HBV-infected partners or through shared needles used for injection drug use. The prevalence of chronic HBV infection is intermediate (2%-7%) in South Central and Southwest Asia, Israel, Japan, Eastern and Southern Europe, Russia, most areas surrounding the Ama-zon River basin, Honduras, and Guatemala. The prevalence of chronic HBV infection is high (>8%) in all socioeconomic groups in certain areas: all of Africa; Southeast Asia, including China, Korea, Indonesia, and the Philippines; the Middle East, except Israel; South and Western Pacific islands; the interior Amazon River basin; and certain parts of the Caribbean (Haiti and the Dominican Republic) (1,2).

Risk for Travelers

The risk of HBV infection for international travelers is generally low, except for certain travelers in countries where the prevalence of chronic HBV infection is high or intermediate. Modes of HBV transmission in areas with high or intermediate prevalence of chronic HBV infection that are important for travelers to consider are contaminated injection and other equipment used for health care-related procedures and blood transfusions from unscreened donors. Unprotected sex and sharing illegal drug injection equipment are also risks for HBV infection in these areas (1,2).

Clinical Presentation

The incubation period of hepatitis B averages 120 days (range 45-160 days). Constitutional symptoms such as malaise and anorexia may precede jaundice by 1-2 weeks. Clinical symptoms and signs include nausea, vomiting, abdominal pain, and jaundice. Skin rashes, joint pains, and arthritis may occur. The case-fatality rate is approximately 1%. Acute HBV infection causes chronic (long-term) infection in 30%-90% of persons infected as infants or children and in 6%-10% of adolescents and adults. Chronic infection can lead to chronic liver disease, liver scarring (cirrhosis), and liver cancer (1).

Prevention

VACCINE

Hepatitis B vaccination is currently recommended for all U.S. residents who work in health-care fields (medical, dental, laboratory, or other) that involve potential exposure to human blood (3,4). All unvaccinated United States children and adolescents (younger than 19 years old) should receive hepatitis B vaccine (5). In addition, unvaccinated persons who have indications for hepatitis B vaccination independent of travel should be vaccinated, such as men who have sex with men, injection drug users, and heterosexuals who have recently had a sexually transmitted disease or have had more than one partner in the previous 6 months (4,6).

Hepatitis B vaccination should be administered to all unvaccinated persons traveling to areas with intermediate to high levels of endemic HBV transmission (i.e., with hepatitis B surface antigen [HBsAg] prevalence >2%). As part of the pre-travel education process, all travelers should be given information about the risks of hepatitis B and other bloodborne pathogens from contaminated medical equipment, injection drug use, or sexual activity, and informed of prevention measures (see below), including hepatitis B vaccination, that can be used to prevent transmission of HBV. Regardless of destination, all persons who might engage in practices that might put them at risk for HBV infection during travel should receive hepatitis B vaccination if previously unvaccinated. It is reasonable for physicians to consider their ability to accurately assess these potential risks when considering if hepatitis B vaccine should be offered. Any adult seeking protection from HBV infection should be vaccinated. Acknowledgment of a specific risk factor is not a requirement for vaccination (4).

Two monovalent hepatitis B vaccines are currently licensed in the United States: Recombivax HB, manufactured by Merck and Co., Inc., and Engerix B, manufactured by GlaxoSmithKline. Vaccines available in the United States use recombinant DNA technology to express HBsAg in yeast, which is then purified from the cells by biochemical and bio-physical separation techniques. The usual schedule of primary vaccination consists of three intramuscular doses of vaccine. The recommended dose varies by product and the recipient’s age (Table 4-7). The vaccine is usually administered as a three-dose series on a 0-, 1-, and 6-month schedule. The second dose should be given 1 month after the first dose; the third dose should be given at least 2 months after the second dose and at least 4 months after the first dose. Alternatively, the vaccine produced by GlaxoSmithKline is also approved for administration on a four-dose schedule at 0, 1, 2, and 12 months. There is also a two-dose schedule for a vaccine produced by Merck & Co., Inc., which has been licensed for children and adolescents 11-15 years of age. Using the two-dose schedule, the adult dose of Recombivax-HB is administered, with the second dose given 4-6 months after the first dose. An interrupted hepatitis B vaccine series does not need to be restarted. A three-dose series that has been started with one brand of vaccine may be completed with the other brand (1,5).

Twinrix, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons 18 years of age or older. Primary immunization consists of three doses, given on a 0-, 1-, and 6-month schedule, the same schedule as that used for single-antigen hepatitis B vaccine (Table 4-5). Twinrix consists of inactivated hepatitis A virus and recombinant HBsAg protein, with aluminum phosphate and aluminum hydroxide as adjuvants and 2-phenoxyethanol as a preservative (1,5).

Clinicians may choose to use an accelerated schedule (for either the hepatitis B vaccine or Twinrix) (i.e., doses at days 0, 7, and 21). The FDA has approved the accelerated schedule for Twinrix, but not for the monovalent hepatitis B vaccine. Persons who receive a vaccination on an accelerated schedule should also receive a booster dose at 1 year after the start of the series to promote long-term immunity (7).

Ideally, vaccination should begin at least 6 months before travel so the full vaccine series can be completed before departure. Because some protection is provided by one or two doses, the vaccine series should be initiated, if indicated, even if it cannot be completed before departure. Optimal protection, however, is not conferred until after the final vaccine dose. There is no interference between hepatitis B vaccine and other simultaneously administered vaccine(s) or with IG. The optimum site of injection in adults is the deltoid muscle. Long-term studies of healthy adults and children indicate that immunologic memory remains intact for at least 15 years and confers protection against chronic HBV infection, even though hepatitis B surface antibody (anti-HBs) levels can become low or decline below detectable levels. For children and adults whose immune status is normal, booster doses of vaccine are not recommended. Serologic testing to assess antibody levels is not necessary for most vaccinees. (See Chapter 8, for a discussion of the hepatitis B immunization schedule for infants who will be traveling [5,8].)

Adverse Reactions

Hepatitis B vaccines have been shown to be very safe for persons of all ages. Pain at the injection site (3%-29%) and elevated temperature higher than 37.7°C (99.9°F) (1%-6%) are the most frequently reported side effects among vaccine recipients. In placebo-controlled studies, these side effects were reported no more frequently among persons receiving hepatitis B vaccine than among those receiving placebo. Among children receiving both hepatitis B vaccine and diphtheria-tetanus-pertussis (DTP) vaccine, these mild side effects have been observed no more frequently than among children receiving DTP vaccine alone. For hepatitis A vaccine (a component of the combination hepatitis A/hepatitis B vaccine Twinrix), the most frequently reported adverse reactions occurring within 3-5 days were soreness or pain at the injection site and headache. No serious adverse events among children or adults that could be definitively attributed to hepatitis A vaccine or increases in serious adverse events among vaccinated persons compared with baseline rates have been identified (1,5).

Precautions and Contraindications

These vaccines should not be administered to persons with a history of hypersensitivity to any vaccine component, including yeast. The vaccine contains a recombinant protein (HBsAg) that is noninfectious. Limited data indicate that there is no apparent risk of adverse events to the developing fetus when hepatitis B vaccine is administered to pregnant women. HBV infection affecting a pregnant woman can result in serious disease for the mother and chronic infection for the newborn. Neither pregnancy nor lactation should be considered a contraindication for vaccination (1,5).

Behavioral preventive measures are similar to those for HIV infection and AIDS. When seeking medical or dental care, travelers should be advised to be alert to the use of medical, surgical, and dental equipment that has not been adequately sterilized or disinfected, reuse of contaminated equipment, and unsafe injecting practices (e.g., reuse of disposable needles and syringes). HBV and other bloodborne pathogens can be transmitted if tools are not sterile or if the tattoo artist or piercer does not follow other proper infection-control procedures (e.g., washing hands, using latex gloves, and cleaning and disinfecting surfaces and instruments). Travelers should be advised to consider the health risks in deciding to get a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced (see Chapter 2).

Treatment

No specific treatment is available for acute illness caused by hepatitis B. Antiviral drugs are approved for the treatment of chronic hepatitis B (9).

References

1. Mast E, Mahoney F, Kane M, et al. Hepatitis B vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th ed. Philadelphia: W.B. Saunders; 2004.
2. Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M. Unsafe injections in the developing world and transmission of bloodborne pathogens: a review. Bull World Health Organ. 1999;77:789-800.
3. CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV and HIV and recommendations for postexposure prophylaxis. MMWR Morbid Mortal Wkly Rep. 2001;50(RR-11):1-54.
4. CDC. 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). MMWR Morbid Mortal Wkly Rep. 1991;40 (RR-13):1-25.
5. CDC. A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part 1: Immunization of Infants, Children, and Adolescents. MMWR Morbid Mortal Wkly Rep. 2005;54(RR16);1-23
6. CDC. Provisional Recommendations for Hepatitis B Vaccination of Adults—October 2005. Available at: http://www.cdc.gov/nip/recs/provisional_recs/hepB_adult.pdf. Accessed 31 October 2006.
7. Bock HL, Loscher T, Scheiermann N, Baumgarten R, Wiese M, Dutz W, et al. Accelerated schedule for hepatitis B immunization. J Travel Med. 1995;2:213-7.
8. European Consensus Group on Hepatitis B Immunity. Are booster immunisations needed for lifelong hepatitis B immunity? Lancet. 2000;355:561-5.
9. Lok AS, McMahon BJ; Practice Guidelines Committee, American Association for the Study of Liver Diseases (AASLD). Chronic hepatitis B: update of recommendations. Hepatology. 2004:39:857-61.

ANTHONY FIORE, BETH BELL

MAP 4-04 Prevalence of chronic infection with hepatitis B virus, by country, 2006

TABLE 4-07. Recommended doses of currently licensed formulations of hepatitis B vaccine