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Recommendations from a national conference on universal vaccination against hepatitis B and hepatitis A in adults.

ABSTRACT

The Centers for Disease Control and Prevention (CDC) estimate that, in the United States, 78,000 people became infected with hepatitis B in 2001 and that 93,000 cases of hepatitis A occurred in 2002. Current recommendations of the CDC's Advisory Committee on Immunization Practices (ACIP) for hepatitis B and hepatitis A vaccination in adults are based on a daunting list of risk groups, many of which overlap. Simplifying vaccination recommendations and using the term "vaccine-preventable hepatitis" (VPH) may encourage practitioners to administer hepatitis B and hepatitis A vaccines to adults. A group of experts in the fields of primary care, gastroenterology, hepatology, infectious and sexually transmitted diseases, human immunodeficiency virus, travel medicine, and public health convened to discuss prevention of hepatitis B and hepatitis A and to develop recommendations for VPH based on available evidence. They concluded that a universal, age-based vaccination strategy would help to increase vaccination rates among adults, thereby decreasing the incidence of hepatitis B and hepatitis A, and that government funding of hepatitis B and hepatitis A vaccination in adults is needed.

KEY WORDS: hepatitis A, hepatitis B, vaccine, prevention, recommendations

DISCLOSURE: The conference at which the summary statements mentioned in this article were developed was an advisory board meeting sponsored by GlaxoSmithKline.

INTRODUCTION

The Centers for Disease Control and Prevention (CDC) estimate that, in the United States. 78,000 people became infected with hepatitis B in 2001. (1) and that 93,000 cases of hepatitis A occurred in 2002. (2) Hepatitis B and hepatitis A vaccines were introduced in the United States in 1981 (1) and 1995, (2) respectively (Table 1). Both vaccines are safe and highly immunogenic. Hepatitis B vaccine is universally recommended for infants, children, and adolescents; hepatitis A vaccine now is recommended for all children 1 year (12-23 months) of age.

In contrast, current recommendations by the Advisory Committee on Immunization Practices (ACID) for vaccination against hepatitis B and hepatitis A in adults are based on a long list of risk groups (Table 2), (4) which makes evaluation of an adult patient a cumbersome process. (5,6) Because people who become infected with hepatitis B and hepatitis A may have risk factors in common, simplifying hepatitis B and hepatitis A vaccine recommendations and using the term "vaccine-preventable hepatitis" (VPH) to refer to hepatitis B and hepatitis A collectively may encourage practitioners to administer hepatitis B and hepatitis A vaccines to adults.

A group of experts in the fields of primary care, gastroenterology, hepatology, infectious and sexually transmitted diseases (STDs), human immunodeficiency virus (HIV), travel medicine, and public health convened to discuss prevention of hepatitis B and hepatitis A. Respected leaders in each field developed summary statements regarding prevention of hepatitis B and hepatitis A as they relate to each expert's respective area of practice. They then presented the rationale for their statements to the other participants.

Following a detailed discussion, the experts came to an agreement on summary statements (Table 3). The conference attendees' main conclusion was that hepatitis B and hepatitis A vaccination should be universally recommended for adults on the basis of age, rather than on presence of risk factors. They acknowledged that, although the incidence of VPH is decreasing, a substantial disease burden remains, and a major obstacle for implementation of a universal vaccination strategy is lack of funding for purchase and administration of vaccines. Regardless of the approach implemented for adult vaccination against hepatitis, the conference attendees agreed that physician, patient, public, and payer education on VPH is necessary. This article summarizes the evidence presented that supports the agreed-on summary statements related to prevention of hepatitis B and hepatitis A.

PRIMARY CARE PERSPECTIVE

Current Hepatitis Vaccination Recommendations

Although safe and effective vaccines to prevent hepatitis B and hepatitis A have been available for many years and the incidence of these diseases has declined since the introduction of the vaccines, hepatitis B and hepatitis A still account for notable morbidity and mortality in the United States (Figure 1). (7) Symptoms of hepatitis A generally do not last longer than 2 months, but they may last up to 6 months in 10% to 15% of patients. (2) Fulminant hepatitis A causes approximately 100 deaths per year in the United States. Chronic infection with hepatitis B virus, however, can result in cirrhosis, chronic liver failure, and hepatocellular carcinoma. As a consequence of increasing hepatitis B vaccine coverage of children and adolescents, the incidence of new infections and acute hepatitis B now is highest in adults. (8) Men experience more infections than women, with the highest rates occurring across the broad age range of 25 to 49 years (Figure 2).

[FIGURES 1-2 OMITTED]

Office-Based Approach to Hepatitis Vaccination

Obstacles to immunization for hepatitis B and hepatitis A in the clinic include cost and lack of reimbursement, (6) inconsistent recommendations for immunization, lack of provider education, and logistical problems such as patient compliance, lack of physician assessment time, (9,10) and lack of standardized documentation forms. Standing orders and consistent recommendations from professional organizations and government agencies may help overcome some of these obstacles, as then have for childhood vaccination. Many excellent resources for implementation of adult vaccination in ambulatory practice exist, (11,12) but most providers are not familiar with them. For instance, the Immunization Action Coalition (IAC) has developed a publication titled Adults Only Vaccination: A Step by Step Guide, which contains information that will help healthcare providers implement adult vaccination services. Additional tools and programs to help physicians initiate vaccine services are needed, ideal programs would provide in-office assistance and training on coding and payment of fees for vaccine services.

GASTROENTEROLOGY AND HEPATOLOGY PERSPECTIVE

Prevention of Hepatitis B and Hepatitis A in Chronic Liver Disease

Hepatitis B and hepatitis A may lead to worse outcomes in patients with chronic liver disease than in otherwise healthy patients. (13-14) Chronic hepatitis B and hepatitis C co-infection is associated with more severe laboratory abnormalities, worse histologic disease, more complications of cirrhosis, and higher incidence of hepatocellular carcinoma." (15-18) In a study of 56 patients with chronic hepatitis C, cirrhosis was found more frequently in patients with both hepatitis B and hepatitis C (56.2%) than in patients with only hepatitis B (12.9%). (16) In another study, Sagnelli and colleagues (19) evaluated 44 patients with hepatitis B. Six (25.6%) of the 21 patients with underlying hepatitis C had a severe clinical presentation, I patient developed fulminant hepatitis and died. A severe clinical presentation was not observed in any of the 20 patients who did not have hepatitis C (P<0.05).

Hepatitis A superimposed on chronic liver disease also is associated with more severe liver disease and a higher fatality rate. (20-23) During the large 1988 outbreak in Shanghai, China, 310,746 cases of hepatitis A occurred after consumption of contaminated shellfish.(23) Fifteen (32%) of the 47 patients who died had underlying hepatitis B or cirrhosis. The case fatality rates of hepatitis A in the United States among patients with chronic hepatitis B and other preexisting liver diseases were calculated to be 11.7% and 28%, respectively, compared with an overall fatality rate of 0.3%. (21)

Based on available evidence, a reasonable approach for protecting patients with chronic liver disease is to administer hepatitis B and hepatitis A vaccines as early as possible in the course of disease. (13) However, in a study of 693 patients with chronic liver disease, only 29% and 28% of patients seeing specialists, and 14% and 5% of patients in primary care offices received hepatitis B and hepatitis A vaccine, respectively. (24) A recommendation for universal vaccination of adults against hepatitis B and hepatitis A would help to ensure that patients with chronic liver disease are appropriately vaccinated. Hepatitis B and hepatitis A vaccines are safe, well tolerated, and have high seroconversion rates in adults with mild-to-moderate chronic liver disease, (14,25-28) although variable efficacy results have been documented in patients with advanced liver disease or after liver transplantation.(25,29-32)

Screening for Hepatitis B and Hepatitis A Antibodies

Because patients with chronic liver disease have a higher prevalence of hepatitis B and hepatitis A antibodies than the general population, prevaccination antibody screening has been demonstrated to be cost effective. (33,34) Patients negative for hepatitis B and hepatitis A antibodies should be vaccinated.

STD AND HIV PERSPECTIVE

Considerations for Hepatitis B and Hepatitis A Vaccination in Patients Being Evaluated for STDs

Substantial overlap of hepatitis B and hepatitis A infection risk exists, especially in persons with or at risk for STDs, in men who have sex with men, and in illicit drug users. (35) Hepatitis B vaccination, but not hepatitis A vaccination, is recommended for all patients being evaluated in STD clinics. Because persons at high risk for VPH as a result of sexual behavior may not make their risk factors known to their physicians, (36-39) protection of these individuals would be maximized by a universal, age-based vaccination strategy.

Several barriers exist to hepatitis immunization in STD clinic settings, with or without use of a combination vaccine. One of the most cogent barriers is lack of funding for vaccination services. In addition, patients may not consider themselves at risk for infection or they may not return to the clinic after vaccination is recommended, and clinics may not have systems in place to ensure vaccination of patients at risk for infection. (4) Promotion of hepatitis B and hepatitis A prevention by use of the term "VPH" may address some of these barriers. Additionally, implementing a universal vaccination policy for adults may help to decrease the stigma associated with vaccination, as well as increase the likelihood that persons without identifiable risk factors are protected.

Hepatitis Immunization for Patients with HIV

Development of hepatitis B or hepatitis A in HIV-positive patients may be more serious than in HIV-negative patients. (41-44) The incidence of hepatitis B is higher in HIV-infected patients than in the general population. (45,46) The liver-related mortality rate among 5293 men who have sex with men was determined to be higher in men co-infected with HIV and hepatitis B (14.2 deaths/1000 person-years) than in those with HIV only (1.7 deaths/1000 person-years: P<0.001). (44) In addition, the duration of hepatitis A viremia was longer in 15 HIV-infected homosexual men (median, 53 days) than in 15 HIV-negative, age-matched controls (median. 22 days: P<0.05). (41)

Hepatitis B and hepatitis A vaccines have been demonstrated to be safe in HIV-infected adults. (47-50) Postel and colleagues (51) presented evidence at the First International Workshop on HIV and Hepatitis Co-Infection in 2004 that response to hepatitis B vaccine is lower when the CD4 cell count is low or viral load is high. Similarly, HIV-infected adults with a CD4 cell count of 200 cells/[mm.sup.3] or higher are more likely to respond to hepatitis A vaccine than patients with a CD4 cell count below 200 cells/[mm.sup.3]. (49) As a means to reduce liver-related complications in HIV-infected patients, hepatitis B and hepatitis A vaccines should be administered to all HIV-infected patients as early as possible in the course of infection as part of a policy of universal vaccination against hepatitis B and hepatitis A in adults.

TRAVEL MEDICINE PERSPECTIVE

Hepatitis B and Travel

The ACIP recommends that travelers who will be in countries with high or intermediate prevalence of hepatitis B and who will have close contact with the local population should receive hepatitis B vaccine. (4) Frequently documented potential risk factors for hepatitis B related to travel are casual sexual activity, medical and dental care, and household exposure to carriers in expatriate communities. (52-54)

Because many travelers do not seek pre-travel medical evaluation early enough before departure, they are unable to receive hepatitis B vaccine according to the recommended vaccination schedule. Fortunately for these travelers, results of immunogenicity studies suggest that accelerated hepatitis B immunization schedules are effective and result in sustainable immunity.(55,56) In one study, a hepatitis B seroprotection rate of 85% was observed 2 months after administration of combination hepatitis A and hepatitis B vaccine to healthy adults at days 0, 7, and 21. (56) A fourth dose of vaccine was given at month 12. Seroprotection rates in both groups increased to 100% by month 13.

Travel-Related Global Epidemiology of Hepatitis A

Various surveys indicate that in the past few decades, the monthly incidence rate for hepatitis A has decreased from 3 to between (1.1 and 1 per 1000 among travelers to developing countries. (57,58) The use of hepatitis A vaccine in the United States since its licensure in 1995 may have contributed to this decrease. (59) Nevertheless, despite recommendations that all travelers to developing countries be immunized against hepatitis A, a recent survey revealed that only 14% of travelers at high risk for hepatitis A departing from John F. Kennedy International Airport in New York were vaccinated. (60)

Because travel may occur unexpectedly, or travelers may be unaware of their risk, universal immunization should be considered to decrease travel-associated hepatitis A. Early vaccination is preferred because of anticipated lifetime risk of exposure. (61)

US Epidemiology of Hepatitis A and Travel by Immigrants Visiting Friends and Relatives

Immigrants and refugees who return to their native countries to visit friends and relatives, as well as migrant workers and orphans adopted from abroad, constitute a high proportion of international travelers. (52) They are at high risk for hepatitis A because many do not consult a physician prior to travel and are likely to have extended stays and close contact with inhabitants of the countries they are visiting. When these travelers return to the United States, they contribute to hepatitis A transmission. Pediatric travelers with undiagnosed hepatitis A pose a particular risk for transmission of the virus among family, caretakers, and play mates. (62) Incorporating hepatitis A vaccine into the adult immunization schedule on a universal basis would decrease the risk of hepatitis A being imported into the United States by such persons.

Hepatitis A Vaccination in the Last-Minute Traveler

The mean incubation period of hepatitis A is 28 days. (2) At the Third European Conference on Travel Medicine in 2002, Van Damme and colleagues (63) reported that most vaccinees develop antibodies within 2 weeks of vaccination. Therefore, it is reasonable to give the first dose of hepatitis A vaccine to travelers shortly before their departure. The second injection should still be given at 6 months to confer long-term immunity. Further support for administering vaccine shortly before travel is provided by demonstration of postexposure protection from hepatitis A vaccine in outbreak situations (64-68) and in reducing household transmission. (69) Despite recommendations that the vaccine be administered 2 to 4 weeks prior to anticipated exposure, (59) current evidence supports efficacy of hepatitis A vaccine in the imminently departing traveler.

PUBLIC HEALTH PERSPECTIVE

The Healthy People 2010 objectives include goals for reducing the incidence of hepatitis B and hepatitis A in the United States. (70) The goals for decreasing hepatitis B incidence in adults aged 19 to 24 years, 25 to 39 years, and 40 years and older are 90% to 2.4 cases per 100,000, 75% to 5.1 cases per 100,000, and 75% to 3.8 cases per 100,000, respectively. The target incidence rate for hepatitis A is 4.5 cases per 100,000 population, a 60% reduction (Table 4).

Increasing public awareness of hepatitis B and hepatitis A as vaccine-preventable diseases should be a part of state and local public health departments' infectious-disease control and prevention programs. Models of effective community-based interventions that raise awareness and increase the number of persons vaccinated should be emulated. A universal, age-based vaccination strategy among adults may help to achieve the national Healthy People 2010 objectives. Routine hepatitis vaccination should be integrated into health-care settings that serve adults, such as STD and HIV testing and treatment facilities, drug treatment centers, travel clinics, needle exchange programs, criminal justice settings, settings serving men who have sex with men, chronic hemodialysis and end-stage renal disease programs, and facilities for developmentally disabled persons. This integration can be accomplished by educating providers, improving communication skills and consumer awareness, creating office systems and immunization registries, providing payment and coverage for vaccination services through sustainable local and federal funding, and routinely assessing performance and quality.

Inmates and staff in correctional systems, especially prisons and jails, have high burdens of risk for and incidence of hepatitis B, (71-74) but the disease burden of hepatitis A remains unmeasured in this setting. Criminal justice systems present an opportunity to immunize high-risk groups against VPH. (75) The CDC recommend hepatitis B vaccine for all adults in prisons, jails, and community corrections settings (including probation, parole, and re-entry programs), and hepatitis A vaccine for adults with risk factors for hepatitis A or those who are likely to experience complications if infected. (71,76) Despite CDC recommendations, barriers to prevention of hepatitis B and hepatitis A in the criminal justice setting exist and include lack of knowledge, funding, and documentation, and insufficient public health collaboration. Implementation of adult vaccination services in criminal justice settings will require both local and federal funding.

Use of the term "VPH" and a universal age-based hepatitis B and hepatitis A vaccination strategy among adults may help expand funding sources, simplify messages, and advance preventive strategies. Providers should be better informed about mechanisms for reimbursement of VPH vaccines and related services. Stronger and consistent guidelines for universal provision of hepatitis vaccines are necessary to obtain coverage from Medicaid and Medicare, and to influence insurance companies to include vaccine purchase and administration in benefits packages. The federal government, through partnerships with agencies such as the Health Resources and Services Administration (HRSA), CDC, Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Minority Health (OMH), and Centers for Medicare and Medicaid Services (CMS) should cover the cost of hepatitis vaccines and related services. For the federal government to provide this funding, restrictions on federal funding must be lifted and collaborative strategies must be implemented. Additional national, state, and local policies should be adopted or mandated to enable communities to exceed the Healthy People 2010 objectives for prevention of hepatitis B and hepatitis A, and specific goals for prevention should be set for high-risk and minority populations to address disparities in access to health care.

DISCUSSION

Existing recommendations for prevention of hepatitis B and hepatitis A in adults are insufficient to substantially reduce their burden of disease, and thus need to be broadened. Current recommendations are risk based. (4) Before the introduction of universal childhood and adolescent hepatitis B immunization recommendations, overall incidence of hepatitis B was high, especially among African Americans. In recent years, however, rates of disease for all races in children and adolescents have converged at a low rate (Figure 3A ). (77) This success was most likely produced by the universal vaccination strategy employed in these age groups. Currently, most of the new cases of hepatitis B occur in adults aged 19 years and older (Figure 2), (78) and the rates among African Americans are almost 3 times those of other racial groups (Figure 3B). This disparity shows no signs of improving under the risk-based vaccination strategy, but this could change with a recommendation for universal vaccination of adults against hepatitis B.

[FIGURE 3 OMITTED]

Many persons who become infected with VPH do not have clearly identifiable risk factors for infection (8,59,72,78,79) or may not confide in their physicians. Furthermore, many physicians remain uncomfortable asking patients about their risk-associated behaviors, particularly those involving sexual expression and illicit drug use. (80-82)

A recent cost-effectiveness study predicted that use of both hepatitis B and hepatitis A vaccines instead of hepatitis B vaccine alone would prevent 2263 cases of hepatitis A, resulting in a 20% decrease in hepatitis A-related hospitalizations, a 19% decrease in liver transplants, and a 17% decrease in death caused by complications of hepatitis A. (83) Costs for treatment of hepatitis A would decline by $2.5 million. The substitution would cost $20,592 per life-year saved, or $13,397 per quality-adjusted life-year (QALY) gained. In comparison, an intervention typically is considered to be cost effective if it costs less than $50,000 per life-year saved or QALY gained. Universally administering hepatitis A vaccine to adults along with hepatitis B vaccine would protect those persons with unidentified risk factors for infection.

CONCLUSIONS

Even though the incidence of hepatitis B and hepatitis A is decreasing, a substantial disease burden remains. Experts in the fields of primary care, gastroenterology, hepatology, infectious diseases, STDs. HIV, travel medicine, and public health who convened to discuss prevention of hepatitis B and hepatitis A agreed that the most practical approach to disease control, in addition to universal childhood vaccination, is universal vaccination among adults.

ACKNOWLEDGMENTS

The authors gratefully acknowledge Jennifer L. Darby, PharmD, of Scientific Therapeutics Information (STI), Inc. Springfield, New Jersey, and thank her for her editorial assistance in preparing this manuscript. Funding for STI activity was provided by GlaxoSmithKline. Additionally, the authors thank the following conference participants for their contribution to development of this manuscript: Stephanie B.C. Bailey. MD, MSHSA; Jack Carrel, MPH; Jeffrey P Davis, MD; Stanley Gall, MD; Elizabeth F. Gondles, PhD; H. Hunter Handsfield, MD; Chantil Jeffreys, RN, MSN, FNP; Elaine C. Jong, MD; Emmet B. Keeffe, MD; Jay S. Keystone, MD, MSc; Daryl T.Y. Lau. MD, MPH; Jeffrey Laurence, MD, Diane C. Peterson; Alonzo Plough. PhD, MPH; Gregory A. Poland, MD; Laurie Schowalter, MPH; Maria Sjogren, MD; and Robert Steffen, MD.

The conference at which the summary statements mentioned in this article were developed was an advisory board meeting sponsored by GlaxoSmithKline.

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Eugene R. Schiff, MD * Bradley A. Connor, MD ([dagger]) Jody H. Hershey, MD, MPH ([double dagger]) Martin C. Mahoney, MD, PhD ([section]) William Schaffner, MD ([paragraph])

* Division of Hepatology, University of Miami Miller School of Medicine, Miami, Florida

([dagger]) Division of Gastroenterology and Hepatology Department of Medicine, Weill Medical College of Cornell University, New, York, New York

([double dagger]) New River Health District, Christiansburg, Virginia

([section]) Department of Health Behavior, Roswell Park Cancer Institute, Buffalo, and Department of Family Medicine, State University of New York at Buffalo, New, York

([paragraph]) Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Table 1. Hepatitis B and Hepatitis A Vaccines Available in the United
States

 Indicated
Antigen Vaccine age group (yr)

Hepatitis B Engerix-B ([dagger]) [less than or equal
 to] 19
 [greater than or equal
 to] 20

 Recombivax-HB ([dagger]) [less than or equal
 to] 19
 [greater than or equal
 to] 20

Hepatitis A and Twinrix ([dagger]) >18
 hepatitis B

Hepatitis A Havrix ([dagger]) 2-18
 [greater than or equal
 to] 19

 Vaqta ([double dagger]) 1-18
 [greater than or equal
 to]19

Antigen Dose and schedule *

Hepatitis B 10 [micro]g at 0, 1, and 6 mo
 20 [micro]g at 0, 1, and 6 mo
 5 [micro]g at 0, 1, and 6 mo
 10 [micro]g at 0, 1, and 6 mo

Hepatitis A and 720 ELU hepatitis A Ag/20 [micro]g
 hepatitis B HBsAg at 0, 1, and 6 mo

Hepatitis A 720 ELU at 0 and 6-12 mo
 1440 ELU at 0 and 6-12 mo
 25 U at 0 and 6-18 mo
 50 U at 0 and 6-12 mo

* Schedules are FDA approved. The text of this article describes
other nonapproved dosing schedules.

([dagger]) Havrix. Engerix-B, and Twinrix are registered trademarks of
GIaxoSmithKline Biologicals, Rixensart, Belgium.

([double dagger]) Vagta and Recombivax-HB are registered trademarks of
Merck & Co., Inc., Whitehouse Station, New Jersey.

Ag=antigen; ELU=enzyme-linked immunosorbent assay units;
HBsAg=hepatitis B surface antigen; U=units.

Table 2. ACIP Recommendations for Hepatitis B and Hepatitis A Vaccine
Use in Adults (4)

Hepatitis B vaccine Hepatitis A vaccine

* Injection drug users * Users of illegal drugs
* Men who have sex with men * Men who have sex with men
* Healthcare and public safety * Persons working with HAV-infected
 workers who have exposure to primates or with HAV in a research
 blood in the workplace; laboratory setting
 persons in training for * Travelers to countries that have
 healthcare professions high or intermediate endemicity
* Travelers who will be in of HAV
 countries with high * Persons with clotting factor
 or intermediate disorders
 prevalence of chronic HBV * Persons with chronic liver
 infection disease
* Patients who receive * Persons who would like to
 clotting factor concentrates obtain immunity to HAV
* Hemodialysis patients
* Persons with >1 sex partner
 during the previous 6 months
* Household contacts and sex
 partners of persons with
 chronic HBV infection
* Clients and staff members of
 institutions for the
 developmentally disabled
* All clients in STD clinics
* Inmates of long-term
 correctional facilities
* Persons seeking protection
 from HBV infection

ACIP=Advisory Committee on Immunization Practices; HAV=hepatitis
A virus; HBV=hepatitis B virus; STD=sexually transmitted disease.

Table 3. National Conference to Reevaluate Prevention of Hepatitis
B and A: Summary of Recommendations on Vaccine-Preventable Hepatitis

* Although the incidence of vaccine-preventable hepatitis (VPH) (ie,
hepatitis B and hepatitis A virus) is decreasing, a substantial
disease burden remains

* The most practical approach to VPH control is universal vaccination
among adults aged 19-50 years of age, in addition to continued
universal childhood hepatitis B vaccination

* Funding (reimbursement, federal support, etc) represents a major
obstacle to implementing universal adult vaccination

* Regardless of the approach to implement adult vaccination
against hepatitis, physician, patient, public, and payer education
on VPH is necessary

Table 4. Healthy People 2010 Objectives for Reduction in Hepatitis B
and Hepatitis A Incidence (71)

 Cases/100,000 population

 Age group (yr) 1997 baseline
Objective

Reduction in 19-24 24.0
 hepatitis B 25-39 20.2
 [greater than 15.0
 or equal to] 40

Reduction in All ages 11.3
 hepatitis A

 Cases/100,000 population

 2010 target Target
Objective reduction (%)

Reduction in 2.4 90
 hepatitis B 5.1 75
 3.8 75

Reduction in 4.5 60
 hepatitis A
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Author:Schiff, Eugene R.; Connor, Bradley A.; Hershey, Jody H.; Mahoney, Martin C.; Schaffner, William
Publication:Journal of Applied Research
Article Type:Report
Geographic Code:1USA
Date:Mar 1, 2007
Words:6670
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