Stephen C. Hadler

Epidemiological serosurvey of Hepatitis B in China-Declining HBV prevalence due to Hepatitis B vaccination

OBJECTIVE To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants. METHODS National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA. FINDINGS The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other). CONCLUSIONS China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

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.

The Prevention of Hepatitis B with Vaccine: Report of the Centers for Disease Control Multi-Center Efficacy Trial Among Homosexual Men

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

Hepatitis A in day-care centers. A community-wide assessment.

We investigated the spread of viral hepatitis in day-care centers in Maricopa County, Ariz. Over a 10-month period, 398 (40 per cent) of 1008 reported cases of hepatitis Type A or viral hepatitis of unspecified type occurred in persons closely associated with day-care centers. Outbreaks of hepatitis comprising 310 cases were identified in 30 of 308 centers in the county. In 28 outbreaks investigated, the majority of symptomatic cases occurred in household contacts or close relatives of children who attended day-care centers, with 16 per cent of the cases occurring in children who attended the centers and 15 per cent occurring in employees. Hepatitis in both employees and household contacts was strongly related to contact with children one to two years of age who attended the centers (P less than 0.001). Day-care centers appear to be important in the spread of hepatitis A in the United States.

Occurrence of hepatitis A, B, and non-A/non-B in the United States: CDC sentinel county hepatitis study I

Abstract To determine the relative occurrence of hepatitis A, B, and non-A/non-B in the United States, serum samples and epidemiologic data were collected from patients with hepatitis in five selected counties. Overall, 41, 33, and 26 percent of the patients had hepatitis A, hepatitis B, and hepatitis non-A/non-B, respectively. The incidence, especially of hepatitis A, varied considerably. All three types of hepatitis occurred more frequently in those 15 to 44 years of age. Hepatitis A predominated in those less than 15 years of age and non-A/non-B predominated in those older than 44 years. There was a male predominance (65 to 62 percent) for hepatitis A and hepatitis B, but non-A/non-B occurred equally in both sexes. There was no seasonal pattern for any type. Risk factors for hepatitis A were previous contact with a patient with hepatitis (26 percent), homosexual (male) preference (15 percent), and day-care center contact (11 percent). For hepatitis B, risk factors included drug use (26 percent), previous contact with an infected person (22 percent), homosexual preference (12 percent), and a health-care occupation (12 percent). For hepatitis non-A/non-B, risk factors included drug use (16 percent), transfusion (12 percent), and previous contact with an infected person (12 percent). Previous hospitalization appeared to be a risk factor for both hepatitis B and hepatitis non-A/non-B.

Occupational risk of hepatitis B infection in hospital workers.

To estimate the risk of hepatitis B virus (HBV) infection among hospital workers, we measured the prevalence of HBV infection in employees in five hospitals in different parts of the country and examined the effect of occupational and non-occupational factors on HBV prevalence. Among 5,697 persons studied, serologic markers of HBV infection were found in 807 (14%). Prevalence of infection was strongly related to race (Asian greater than Black greater than White), sex (male greater than female) and increasing age. Risk related to health occupation, studied by examining the change in HBV prevalence with duration in occupational group, was most strongly correlated with frequency of contact with blood during work. Workers having frequent blood contact had the highest estimated infection rate (1.05 per 100 person-years) and those with moderate contact an intermediate infection rate, compared to a negligible infection rate in workers with no blood contact. Frequency of needle accidents had an independent, positive effect on HBV infection rates, while degree of patient contact had no effect. Infection risk was uniform among all hospitals for groups with frequent blood contact. Among different occupation groups, risk of HBV infection also correlated closely with degree of blood-needle contact during daily work. This study provides a general approach to assessing risk of HBV infection in hospital personnel, and indicates that risk may be most easily estimated by quantitating degree of blood-needle contact during daily work.

An outbreak of hepatitis B in a dental practice.

In September 1978, cases of hepatitis B in two patients treated by the same dentist led to investigation of a dental practice in Baltimore, Maryland. The dentist had had acute hepatitis B in June 1978 and had remained positive for hepatitis B surface antigen and hepatitis B e antigen over the ensuing 6 months. He had continued to work while infected, wearing surgical gloves to minimize the risk of transmitting infection. Serologic follow-up of 764 patients showed that a total of six patients, three of whom were symptomatic, had developed hepatitis B infection after dental treatment. All six were among a group of 395 patients treated before the dentist began wearing gloves. In this group, patients having highly traumatic dental work (attack rate 6.9%) were at significantly higher risk than patients having either less traumatic work (attack rate 0.5%) or nontraumatic work (attack rate = 0, p less than 0.02). None of 369 patients treated only when the dentist wore gloves became infected, suggesting that gloves could reduce the risk of virus transmission by the dentist.

Pertussis control: time for something new?

Childhood acellular pertussis vaccines were licensed and implemented in the US in the 1990s following an effort to improve on the safety profile of whole-cell vaccines. However, waning of immunity from acellular vaccines may be driving the recent resurgence of pertussis, raising the need to consider new prevention strategies.

Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians

In a large hepatitis B prevention programme, hepatitis B vaccine was given in standard doses to greater than 1000 susceptible Yucpa Indians between 1983 and 1985. Thirteen months after the programme began, 373 vaccine recipients were tested using commercial radioimmunoassay to titre antibody response to the vaccine. Because of logistic difficulties, only 32% had received vaccine by the recommended schedule (second and third doses at one and six months after the first, respectively). The second and third doses were received early by 4 and 31%, respectively, and 27 and 16% received these doses later than intended. Overall response to vaccine was excellent: 98% of vaccinees developed anti-HBs greater than 10 mIU (geometric mean titre 688 mIU). Multivariate analysis showed that the response to vaccination was inversely related to the age of the vaccinee and directly related to the timing of the third vaccine dose. In particular, those receiving the third vaccine dose late (greater than 7 months after the first dose) developed antibody titres two-fold higher than those receiving the third dose on schedule (p less than 0.01). The response to vaccination was not significantly related to the timing of the second dose. A satisfactory response was obtained with various schedules of dose timing, including early second and third doses, late second and third doses and late second but normal third doses. These findings suggest that the response to hepatitis B vaccine is not highly dependent on timing of vaccine doses and that modest alterations in timing of doses, such as those necessary to integrate hepatitis B vaccine with other childhood vaccines, do not affect the excellent response to this vaccine.

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.