Francisco Averhoff

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.

A middle school immunization law rapidly and substantially increases immunization coverage among adolescents.

OBJECTIVES This study assessed the effectiveness of a middle school vaccination requirement for raising second-dose measles, mumps, and rubella vaccine and hepatitis B vaccine coverage among adolescents. METHODS Random-digit-dialed telephone surveys were conducted before (1998) and after (1999) the implementation of a vaccination requirement for entry into the seventh grade in San Diego, Calif. RESULTS Vaccination coverage was higher among children subject to the vaccination requirement (seventh-grade students; 60%) than among fifth- and sixth-grade students 1 year before the requirement (13%, P <.001), and 8th- through 12th-grade students not subject to the requirement (27%, P <.0001). CONCLUSIONS Middle school-entry vaccination requirements can rapidly and substantially raise vaccination coverage among students subject to the law.

Outbreak of Hepatitis A among Men Who Have Sex with Men: Implications for Hepatitis A Vaccination Strategies

Between November 1998 and May 1999, 136 cases of hepatitis A were reported in Columbus, Ohio. Eighty-nine (65%) case patients were reinterviewed. Of 74 male case patients, 47 (66%) were men who have sex with men (MSM). These 47 MSM were compared with 88 MSM control subjects, to identify risk factors for infection and potential opportunities for vaccination. During the exposure period, 6 (13%) case patients reported contact with a person who had hepatitis A, compared with 2 (2%) control subjects (odds ratio, 6.15; 95% confidence interval, 1.04-48.02); neither number of sex partners nor any sex practice was associated with illness. Most case patients and control subjects (68% and 77%, respectively) saw a health care provider at least annually, and 93% of control subjects reported a willingness to receive hepatitis A vaccine. MSM are accessible and amenable to vaccination; increased efforts are needed to provide vaccination, regardless of reported sex practices.

Genetic relatedness of hepatitis A virus isolates during a community‐wide outbreak

In 1993–94, a community‐wide outbreak of hepatitis A occurred in Stanislaus County, California. Stool specimens collected from a sample of 33 case patients were used to evaluate the duration of hepatitis A virus (HAV) excretion and the genetic relatedness of HAV isolates. Twenty‐four percent of the patients had a stool sample positive for HAV antigen by enzyme immunoassay, whereas 91% had at least one stool positive for HAV RNA by RT‐PCR amplification. Children were found to excrete low levels of HAV RNA for up to 10 weeks after the onset of symptoms. Analysis of the HAV VP1 amino terminus and VP1/P2A regions showed that a limited number of HAV isolates circulated during the epidemic and the majority of the cases were infected with the same strain. J. Med. Virol. 62:144–150, 2000.

Household Responses to School Closure Resulting from Outbreak of Influenza B, North Carolina

Parents accepted school closure during an outbreak, but children’s presence in other public settings has implications for pandemic planning.

Vaccine coverage levels after implementation of a middle school vaccination requirement, Florida, 1997-2000

Objective. Little information is available about the effectiveness of school entry vaccination requirements at the middle school level. This study examined coverage levels among students entering seventh grade in Florida following implementation of a school entry vaccination requirement in 1997. Methods. The authors analyzed county-specific vaccination coverage levels (three doses of hepatitis B vaccine, a second dose of measles, mumps, and rubella [MMR] vaccine, and a booster dose of tetanus and diphtheria toxoids [Td]) among students entering public and private schools in Florida from 1997 through 2000. In 1998, a survey of all county health departments was conducted, and the resulting data were linked to county-specific vaccination rates. Results. During the 1997–1998 school year, the first year the requirement went into effect, at school entry 121,219 seventh-grade students (61.8%) were fully vaccinated, 72,275 seventh grade students (36.9%) lacked one or more doses of vaccine but were considered in process, 1,817 were non-compliant (0.9%), and 763 had medical or religious exemptions (0.4%). In the 2000–2001 school year, the proportions of students reported fully vaccinated at school entry had increased to 66%. Most of this change was related to an increase in hepatitis B coverage. There was a significant inverse relationship between the proportion of students fully vaccinated and the size of the countys seventh grade population. Conclusions. The seventh grade vaccination entry requirement was associated with sustained high levels of vaccination coverage. Passing a school entry vaccination requirement appears may be sufficient to increase coverage, but other strategies may be required to achieve full immunization of middle school students.

Occupational Exposures and Risk of Hepatitis B Virus Infection Among Public Safety Workers

We conducted a questionnaire and seroprevalence survey to determine the frequency and type of occupational exposures (OEs) and the risk of hepatitis B virus (HBV) infection experienced by public safety workers (PSWs). Of the 2910 PSWs who completed the survey, 6.8% reported at least one OE in the previous 6 months, including needlestick (1.0%), being cut with a contaminated object (2.8%), mucous membrane exposure to blood (0.9%), and being bitten by a human (3.5%). The rate of OE varied by occupation with 2.7% of firefighters, 3.2% of sheriff officers, 6.6% of corrections officers, and 7.4% of police officers reporting ≥1 OE (P < 0.001). The HBV infection prevalence was 8.6%, and after adjustment for age and race, it was comparable to the overall US prevalence and did not vary by occupation. By multivariate analysis, HBV infection was not associated with any OEs, but it was associated with older age, being nonwhite, and a previous history of a sexually transmitted disease. This study demonstrated that although OEs are not uncommon among PSWs, HBV infection was more likely to be associated with nonoccupational risk factors. Administration of hepatitis B vaccine to PSWs early in their careers will prevent HBV infection associated with occupational and non-OEs.

The impact of hepatitis B vaccine in China and in the China GAVI Project

The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB) vaccine to infants born in the less developed areas of China including the Western provinces and poverty counties of Middle provinces, to prevent the consequences of hepatitis B virus infection. By 2009, the project areas had raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90% among infants, comparable to those in wealthier Eastern provinces, and reduced HBV prevalence to <1% among children in these areas. We estimated the impact in disease prevented by HB vaccine in China between 1992, when the vaccine was routinely recommended, and 2009, and in CGP areas for the years 2003-2009, when the CGP was active. A published model was used to estimate the burden of chronic and acute HBV infection and death prevented due to HB vaccination in China and the CGP areas using data from national serosurveys in China in 1992 and 2006, and HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling to estimate vaccine coverage nationally, regionally, and CGP areas. We also estimated the incremental impact of the CGP on HB vaccine coverage in those underserved areas. Our findings suggest that between 1992 and 2009, HB vaccination in China has prevented 24 million chronic HBV infections and 4.3 million future deaths due to cirrhosis, hepatocellular carcinoma and acute hepatitis. During the CGP between 2003 and 2009, an estimated 3.8 million chronic HBV infections and 680,000 deaths were prevented in CGP areas. We found that the CGP funding increased HB vaccine coverage in project areas by 4-15% for HB3 and 4-27% for timely birth dose beyond the coverage expected without the CGP. The CGP represents a highly successful public health collaboration between the national government and international partners.

Effectiveness of a school district closure for pandemic influenza A (H1N1) on acute respiratory illnesses in the community: a natural experiment

BACKGROUND Following detection of pandemic influenza A H1N1 (pH1N1) in Dallas/Fort Worth, Texas, a school district (intervention community, [IC]) closed all public schools for 8 days to reduce transmission. Nearby school districts (control community [CC]) mostly remained open. METHODS We collected household data to measure self-reported acute respiratory illness (ARI), before, during, and after school closures. We also collected influenza-related visits to emergency departments (ED(flu)). RESULTS In both communities, self-reported ARIs and ED(flu) visits increased from before to during the school closure, but the increase in ARI rates was 45% lower in the IC (0.6% before to 1.2% during) than in the CC (0.4% before to 1.5% during) (RRR(During)(/Before) = 0.55, P < .001; adjusted OR(During/Before) = 0.49, P < .03). For households with school-aged children only (no children 0-5 years), IC had even lower increases in adjusted ARI than in the CC (adjusted OR(During/Before) = 0.28, P < .001). The relative increase of total ED(flu) visits in the IC was 27% lower (2.8% before to 4.4% during) compared with the CC (2.9% before to 6.2% during). Among children aged 6-18 years, the percentage of ED(flu) in IC remained constant (5.1% before vs 5.2% during), whereas in the CC it more than doubled (5.2% before vs 10.9% during). After schools reopened, ARI rates and ED(flu) visits decreased in both communities. CONCLUSIONS Our study documents a reduction in ARI and ED(flu) visits in the intervention community. Our findings can be used to assess the potential benefit of school closures during pandemics.

Implementing a seventh grade vaccination law: school factors associated with completion of required immunizations.

OBJECTIVES We investigated school factors associated with successful implementation of a seventh grade vaccination requirement. METHODS The proportion of students vaccinated with hepatitis B vaccine and measles containing vaccine was determined from records of schools in San Diego County, California. A school survey identified compliance strategies. Analysis identified factors associated with coverage. RESULTS In October 1999, 67.2% of 38,875 students had received the required vaccine doses. Of 315 schools, coverage was less than 40% in 60 schools and exceeded 80% in 111 schools. Factors associated with high coverage included private schools, early and frequent notice to parents, and, for public schools, higher overall socioeconomic status of students. CONCLUSIONS In preparation for a middle school vaccination requirement, early and frequent notification of parents improves coverage. Schools with a high percentage of low socioeconomic status students may require extra resources to support implementation.