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Hepatitis B

Originally known as serum hepatitis, hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa. Hepatitis B is recognized as endemic in China and various other parts of Asia. Over one-third of the world's population has been or is actively infected by hepatitis B virus (acronym HBV). more...

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Molecular biology

The hepatitis B virus is a member of the Hepadnavirus family. It consists of a proteinaceous core particle containing the viral genome in the form of double stranded DNA and an outer lipid-based envelope with embedded proteins. The envelope proteins are involved in viral binding and release into susceptible cells. The inner capsid relocates the DNA genome to the cell's nucleus where viral mRNAs are transcribed. Three subgenomic transcripts encoding the envelope proteins are made, along with a poorly understood transcript encoding the X protein, whose function is still under debate. A fourth pre-genomic RNA is transcribed, which is exported to the cytosol and translates the viral polymerase and core proteins. Polymerase and pre-genomic RNA are encapsidated in assembling core particles, where reverse transcription of the pre-genomic RNA to genomic DNA occurs by the polymerase protein. The mature core particle then exits the cell via normal secretory pathways, acquiring an envelope along the way.

Hepatitis B is one of a few known non-retroviral viruses which employ reverse transcription as part of its replication process. Other viruses which use reverse transcription include HTLV or HIV, the virus that causes AIDS, but HIV and hepatitis B are not related. Hepatitis B's genome is DNA, and reverse transcription is one of the latter steps in making new viral particles, whereas HIV has an RNA genome and reverse transcription is one of the first steps in replication.

Transmission

Hepatitis B is largely transmitted through exposure to bodily fluids containing the virus. This includes unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, vertical transmission from mother to child during childbirth, and so on. The primary method of transmission depends on the prevalence of the disease in a given area. In low prevalence areas, such as the continental United States, IV drug abuse and unprotected sex are the primary method. In moderate prevalence areas, the disease is predominantly spread among children. In high prevalence countries, such as China, vertical transmission is most common. Without intervention, a mother who is positive for the hepatitis B surface antigen confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for the hepatitis B e antigen.

Roughly 16-40% of unimmunized sexual partners of individuals with hepatitis B will be infected through sexual contact. The risk of transmission is closely related to the rate of viral replication in the infected individual at the time of exposure.

Clinical consequences and complications

Hepatitis B virus infection may either be acute (self-limited) or chronic (long-standing). Persons with self-limited infection clear the infection spontaneously within weeks to months.

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Hepatitis B in women: domestically and internationally.
From Emerging Infectious Diseases, 11/1/04 by Cindy Weinbaum

Globally, hepatitis B virus (HBV) infection is a major cause of infectious disease-related death, causing approximately 620,000 deaths annually. Without hepatitis B vaccination, an estimated 1.4 million HBV-related deaths would occur in the 2000 birth cohort over the lifetime of the cohort. HBV infections acquired in the perinatal and early childhood periods account for 21% and 48%, respectively, of HBV-related deaths worldwide. Thus, routine vaccination of infants and children serves as the basis for a global hepatitis B prevention program.

In 1992, the World Health Organization recommended that hepatitis B vaccine be included in childhood immunization programs in all countries, but because of financial constraints, many countries were unable to initially implement this recommendation. In 1999, a global initiative began to make hepatitis B vaccine available to children living in 69 of the world's poorest countries, and by the end of 2003, routine childhood hepatitis B vaccination was included in national immunization programs in >151 countries. However, many countries, mainly in sub-Saharan Africa, have not yet introduced the vaccine, and coverage with the three-dose vaccination series remains low in many countries that have introduced the vaccine. When all countries have introduced the vaccine and coverage with the three-dose vaccination series reaches 90%, up to 84% of global HBV-related deaths will be prevented.

Hepatitis B in the United States

In the United States, an estimated 5% of the civilian, noninstitutionalized population has serologic evidence of past or present HBV infection, and 0.4%-0.5% have chronic infection and are the primary source of infection for others. From 1990 through 2002, the incidence of reported acute hepatitis B declined 67%. The incidence of acute hepatitis B among men has been consistently higher than among women. In 1990, the incidence among men and women was 9.8 and 6.3 per 100,000, respectively; in 2002, the incidence was 3.7 and 2.2 per 100,000, respectively. Overall, incidence among women has declined more than among men. Trends in acute hepatitis B reflect poor vaccination coverage among persons who engage in high-risk behavior.

Persons at high risk for HBV infection often seek health care in settings in which vaccination services could be provided. During 1996-1998, approximately half of persons with reported acute hepatitis B previously had been treated for a sexually transmitted disease (STD) or incarcerated: 89% of injection drug users, 35% of men who have sex with men, and 70% of persons with multiple sex partners with reported acute hepatitis B had been previously incarcerated or treated for an STD. Both STD clinics and correctional facilities are settings in which hepatitis B vaccination services are recommended.

Programmatic Success in High Risk Settings

In August 1999, Denver Public Health (DPH) began offering hepatitis B vaccine to adults at high risk in the public STD clinic. Initial funding for the vaccine was first allocated by the Denver City Council. Patients were asked if they had a history of hepatitis B vaccination or disease and questioned about risk behavior; no serologic screening was done. The selective vaccination process was cumbersome, and clinicians required frequent reminders to implement it. Of clients seen in the STD clinic, 58% accepted the vaccine and were directed to receive it in the immunization clinic in the same building. Of clients who agreed to the free vaccine, 29% left before receiving it. Procedures changed when additional funding was secured in January 2002. Client selection was discontinued, and all clients of the STD and HIV Counseling and Testing clinics were offered vaccine, which increased its initial acceptance to 77%. Vaccination rates were further improved by having personnel available to vaccinate clients on site, before they left the clinic.

DPH used a vaccine registry, adapted from one implemented to track pediatric vaccinations, to assess clients' vaccination status before doses were given. The results indicated that clients were not differentiating between vaccinations and various other tests or medications in self-reporting of immunization status. Use of the vaccine registry was crucial for evaluating completion rates and eliminating revaccination of persons already immunized.

A highly successful hepatitis B vaccination program can be established within another public health infrastructure. The process requires commitment from all involved programs because changes in service delivery are needed to accommodate vaccination. The largest issue confronting programs is continued funding for vaccine.

Address for correspondence: Cindy Weinbaum, Centers for Disease Control and Prevention, 1600 Clifton Road., Mailstop G37, Atlanta, GA 30033, USA; fax: 404-371-5488; email: cweinbaum@cdc.gov

Cindy Weinbaum, * Susan Goldstein, * and Julie Subiadur ([dagger])

* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; and ([dagger]) Denver Public Health Department, Denver, Colorado, USA

COPYRIGHT 2004 U.S. National Center for Infectious Diseases
COPYRIGHT 2004 Gale Group

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