Patrick J. Coleman

Long-Term Immunogenicity and Efficacy of Hepatitis B Vaccine in Homosexual Men

To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed.

Immunogenicity of Hepatitis B Vaccines Implications for Persons at Occupational Risk of Hepatitis B Virus Infection

OBJECTIVE To assess risk factors for decreased immunogenicity among adults vaccinated with hepatitis B vaccine and to determine the importance of differences in immunogenicity between vaccines among health care workers (HCWs). DESIGN Randomized clinical trial and decision analysis. PARTICIPANTS HCSw. MAIN OUTCOME MEASURES Development of seroprotective levels of antibody to hepatitis B surface antigen (anti-HBs) and the number of expected chronic hepatitis B virus (HBV) infections associated with lack of protection. RESULTS Overall, 88% of HCWs developed seroprotection. Risk factors associated with failure to develop seroprotection included increasing age, obesity, smoking and male gender (P < .05). Presence of a chronic disease was associated with lack of seroprotection only among persons > or = 40 years of age (P < .05). The two vaccines studied differed in their overall seroprotection rates (90% vs. 86%; P < .05), however, this difference was restricted to persons > or = 40 years of age (87% vs. 81%; P < .01). Among HCWs > or = 40 years of age, the decision analysis found 44 (0.34/100,000 person-years) excess chronic HBV infections over the working life of the cohort associated with use of the less immunogenic vaccine compared to the other. CONCLUSIONS He patitis B vaccines are highly immunogenic, but have decreased immunogenicity associated with increasing age, obesity, smoking, and male gender; and among older adults, the presence of a chronic disease. One of the two available vaccines is more immunogenic among older adults; however, this finding has little clinical or public health importance. Hepatitis B vaccines should be administered to persons at occupational risk for HBV infection early in their career, preferably while they are still in their training.

Incidence of Hepatitis B Virus Infection in the United States, 1976–1994: Estimates from the National Health and Nutrition Examination Surveys

Precise estimates of the incidence of hepatitis B virus (HBV) infection are required to assess the impact of immunization and other prevention strategies in the United States. Race- and age-specific prevalence data obtained from the second and third National Health and Nutrition Examination Surveys (NHANES II, 1976-1980, and NHANES III, 1988-1994) were used to estimate the annual incidence of HBV infection by catalytic modeling. During the period covered by NHANES II, an estimated 323,462 persons were infected annually, and 334,863 were infected annually during the period covered by NHANES III. No statistically significant declines in prevalence of HBV infection occurred between the two surveys, a period during which hepatitis B vaccination targeted only limited numbers of high-risk adults.

Epidemiology of hepatitis A: seroepidemiology and risk groups in the USA.

Surveillance and seroepidemiological data are important in determining optimal hepatitis A vaccine strategies. In the USA, after a decade of declining rates, reported hepatitis A rates gradually increased from 9.2 cases per 100,000 population in 1983 to a peak of 14.4 per 100,000 in 1989. In 1991, 23,144 cases were reported, for a rate of 9.1 per 100,000. Since 1983, rates in males have been consistently 20% higher than in females. Rates in children, adolescents and adults up to 39 years old have been roughly equivalent and approximately threefold higher than for persons > or = 40 years old. Among reported cases in 1989, the most commonly reported risk factor was personal contact with a hepatitis A case (26%), followed by employment or attendance at a day-care centre (14%), a history of injecting drug use (11%), a history of recent international travel (4%), and association with a suspected food or waterborne outbreak (3%). Of cases, 42% had no known risk factor for infection. The prevalence of antibody to hepatitis A virus in the general US population was 38.2%, based upon testing of 9516 participants from the second National Health and Nutrition Examination Survey conducted from 1976 to 1980. Prevalence increased steadily with age, ranging from 11% in persons < 5 years of age to 74% in persons > or = 50 years old. Because some groups may be difficult to vaccinate prior to disease exposure (contacts of cases) or are difficult to reach (drug users or persons with unidentified risk), a selected risk group vaccination strategy may not be successful in reducing the disease burden in the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter study of hepatitis C virus infection in chronic hemodialysis patients and hemodialysis center staff members.

Between April 1990 and December 1991, 499 (65%) of 767 patients and 142 (59%) of 239 staff members from 11 chronic hemodialysis centers in different geographic regions of the United States participated in a multicenter prospective cohort study that determined the prevalence and incidence of antibody to hepatitis C virus (anti-HCV) and evaluated their risk factors for HCV infection. Serum samples were tested for anti-HCV by enzyme immunoassay and HCV neutralization assay at baseline and 9 and 18 months later. Collected data included patient and staff demographics, number of years a patient had been on dialysis or staff were employed in the dialysis field, history and dates of blood transfusions, history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV was detected in 52 (10%) of 499 patients and in two (1%) of 142 staff members. Logistic regression analysis revealed that in patients, an anti-HCV-positive test was associated with length of time on dialysis (3 or more years), history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV positivity was not associated with history of blood transfusions, race, gender, or age. In patients, the cumulative incidence of HCV infection over an 18-month period was 4.6%. Throughout the 18-month follow-up period, no staff members became anti-HCV positive. The association between anti-HCV positivity and increasing patient years on dialysis may reflect the cumulative risk of exposure to infectious blood in the dialysis environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for hepatitis C virus infection among health care personnel in a community hospital

OBJECTIVE To determine the prevalence of and risk factors for antibody to the hepatitis C virus in hospital employees. METHODS Retrospective testing of serum samples obtained from 1677 hospital employees during a prehepatitis B vaccination program in a private teaching community hospital. RESULTS Twenty-three employees (1.4%) were found to have antibody to hepatitis C virus. The prevalence of antibody to hepatitis C virus was higher in blacks (3.4%) than in whites (1.1%, p = 0.03) and Hispanics (2.6%, p = 0.88). In a logistic regression model, factors significantly associated with antibody to hepatitis C virus seropositivity included antibody to hepatitis B core antigen (p = 0.002), a history of blood transfusion (p = 0.03), and needlestick injuries (p = 0.04). CONCLUSION Although the prevalence of antibody to hepatitis C virus in health care workers was not high, needlestick injuries were associated with an increased risk for acquiring hepatitis C virus infection.

Intradermal hepatitis B vaccination in a large hospital employee population

The intradermal route of hepatitis B vaccine administration has been tested in several clinical trials and has produced various degrees of immunogenicity, but usually among small groups of participants. To assess more adequately the immunogenicity of hepatitis B vaccine using the intradermal route, the Centers for Disease Control conducted a clinical trial among 425 well health-care workers in a hospital setting. Participants were randomly assigned to one of two treatment groups: those receiving a 20 micrograms intramuscular injection, and those receiving a 2 micrograms intradermal injection. Participants received the plasma-derived hepatitis B vaccine by the standard schedule at 0, 1 and 6 months, and serum samples were collected at 3, 8, 12 and 24 months after the first dose. Antibody response rates (anti-HBs titre greater than or equal to 10 sample ratio units by radioimmunoassay) for the intradermal vaccination group were consistently lower than those for the intramuscular vaccination group at each testing interval. The differences were greatest for the 3-month test and decreased over time. Geometric mean titres for anti-HBs for the intradermal group were significantly lower than those for the intramuscular group at the 8-month test point. In addition to inoculation route, factors of gender, smoking and age were found to have significant effects on immune response. The results suggest that intradermal vaccination with hepatitis B vaccine may be appropriate under certain conditions and for certain population subgroups.

Risk of infection with hepatitis A, B or C, cytomegalovirus, varicella or measles among child care providers

BACKGROUND Employment as a child care provider has been suggested as an indication for hepatitis A virus (HAV) immunization; however, whether this occupational group is at increased risk of HAV infection is not well-defined. METHODS We obtained sera samples for testing for antibodies to hepatitis A, B and C, cytomegalovirus, varicella and measles from a sample of child care providers in King County, WA, and administered a questionnaire to assess employment characteristics and other potential risk factors for infection. We also compared the anti-HAV seroprevalence among providers with that of subjects in the Third National Health and Nutrition Survey, representative of the US general population. RESULTS Thirteen percent (48 of 360) of providers were anti-HAV-positive (46% (22 of 47) of foreign born vs. 8% (26 of 313) of US-born (P < 0.001)). In multivariate analysis anti-HAV seropositivity was associated with foreign birth, age, income and Hispanic ethnicity but was not associated with characteristics of employment. Seroprevalence among US-born providers tended to be lower than that among Third National Health and Nutrition Survey subjects of similar age, sex, race and income. Sixty-two percent of providers were seropositive to cytomegalovirus, which was associated with nonwhite race, changing diapers > or = 3 days/week while at work and having a child in the household. Antibody prevalence was 1.4% to hepatitis B core antigen, 0.6% to hepatitis C, 94% to measles and 98% to varicella. CONCLUSIONS The anti-HAV prevalence among US-born providers was low, and seropositivity was not associated with employment characteristics, indicating that occupational exposure to HAV is uncommon under non-outbreak circumstances.

Viral Hepatitis in North America

Hepatitis A (HA) accounts for 32% of the acute viral hepatitis in the United States, hepatitis B (HB) for 43%, and hepatitis C (HC) for 21%. Community-wide epidemics of HA contribute significantly to the burden of disease, as well as occasional day-care center and common-source outbreaks; international travel accounts for a small proportion of cases. Up to 40% of cases have no known risk factor. Targeting selected risk groups to receive HA vaccination probably will have little impact on overall disease rates. Most acute HB occurs in young adults, with gt;50% resulting from sexual activity, but 20–30% of chronic infections are the result of infection acquired in infancy and childhood. Efforts to vaccinate persons in major risk groups have met with limited success; therefore, the current strategy emphasizes the integration of HB vaccine into routine childhood immunization schedules. Most HC is acquired outside the transfusion setting. Since both chronic liver disease and persistent infection develop in a high proportion of patients, there is a need for preventive and therapeutic measures for persons in all risk groups.