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Epidemiologic Notes and Reports Inadequate Immune Response Among Public Safety Workers Receiving Intradermal Vaccination Against Hepatitis B -- United States, 1990-1991

The Immunization Practices Advisory Committee (ACIP) recommends that hepatitis B vaccine be administered by the intramuscular (IM) route (1). However, since November 1990, public safety departments have reported to CDC at least four instances of poor immune response among public safety workers vaccinated against hepatitis B by the intradermal (ID) route of administration.

Report 1. In December 1990, the fire and police departments in Tuscaloosa, Alabama, contracted with a private company to have hepatitis B vaccine administered to all employees. The cost of vaccination was $100 per employee; this fee included three doses of vaccine and postvaccination testing but did not include the costs of phlebotomy or additional doses of vaccine. All employees were vaccinated with 0.1 mL ( the ACIP-recommended IM dose) of recombinant hepatitis B vaccine by the ID route at months 0, 1, and 6; postvaccination serum samples were obtained 4-6 weeks after the third dose had been administered.

A total of 226 employees were vaccinated; of these, 213 (94%) were men. Forty-nine (22%) were aged 23-29 years; 98 (43%), 30-39 years; and 79 (35%), greater than or equal to 40 years. The contractor reported that, of the 226 employees, 108 (48%) had adequate serologic responses* to the three-dose series. The contractor also reported that vaccinees less than 40 years of age were more likely to have responded adequately than those greater than or equal to 40 years of age (56% vs. 34%; p less than 0.01; chi-square test). The contractor offered to administer two additional doses by the ID route to nonresponders for $70 per person, thereby increasing the potential cost of vaccination for all employees to an average of $137 per vaccinee.

Report 2. During 1989, a public safety department in Fairhaven, Massachusetts, contracted with a private company to have public employees (including fire, police, and visiting nurse personnel) vaccinated with recombinant hepatitis B vaccine. The department reported that of 62 employees who were vaccinated, 30 (48%) adequately responded to three 0.1-mL doses administered by the ID route. Of the 32 nonresponders, 31 (97%) developed protective levels of antibody to hepatitis B surface antigen (anti-HBs) after vaccination with an additional 1.0-mL dose by the IM route. The average cost per employee for the vaccine program was $130, including the IM dose for nonresponders and postvaccination testing.

Report 3. In April 1989, a fire department in Quincy, Illinois, contracted with a private company to have recombinant hepatitis B vaccine administered to employees by the ID route using three 0.1-mL doses. The average age of the 59 vaccinated employees was 40 years; all were male. The contractor reported that 14 (24%) developed protective levels of anti-HBs. Nonresponders were vaccinated with one additional dose by the ID route; if adequate antibody titers did not develop, an additional dose by the same route was administered. Of the 45 employees who were vaccinated with either one or two additional doses, 41 (91%) developed protective levels of anti-HBs. The remaining four nonresponders were vaccinated with a second three-dose series by the ID route; postvaccination test results are pending. The second series cost an additional $105 for each of the four nonresponders; the overall average cost for the vaccination program was $132 per employee.

Report 4. In 1988, the Santa Barbara, California, fire department contracted with a private company to have hepatitis B vaccine administered to employees. The contractor vaccinated 44 of the 87 male and all nine female employees (average age of vaccinees: 33 years) with three 0.1-mL doses of recombinant hepatitis B vaccine by the ID route. Postvaccination testing indicated that 21 (40%) employees developed protective levels of anti-HBs. Because of the low response rate after ID vaccination, the remaining 43 male employees (average age: 33 years) were vaccinated by the IM route; after three vaccine doses, protective levels developed in 41 (95%) persons. Reported by: M Tant, Tuscaloosa Fire Dept, Tuscaloosa, Alabama. R Gerkin, MD, Phoenix Fire Dept, Phoenix; SJ Englender, MD, State Epidemiologist, Arizona Dept of Health Svcs. M Lugo, Santa Barbara Fire Dept, Santa Barbara; RR Roberto, MD, GW Rutherford, MD, State Epidemiologist, California Dept of Health Svcs. P Fowle, Fairhaven Board of Health, Fairhaven, Massachusetts. W Twaddle, J Beebe, Fire Dept, Quincy, Illinois. Hepatitis Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Infection with hepatitis B virus is an occupational risk for persons who have direct contact with blood or body fluids (2). CDC has recommended that health-care workers who have contact with blood or body fluids use universal precautions and that workers with occupational exposure to blood be vaccinated with hepatitis B vaccine (3). Regulations regarding these recommendations have been proposed by the Occupational Safety and Health Administration (4).

Some organizations have attempted to decrease the cost of employee hepatitis B vaccination by administering the recommended IM vaccine dose by the ID route; however, hepatitis B vaccine is not licensed by the FDA for ID administration. In addition, ACIP recommends that hepatitis B vaccine be administered by the ID route only when a research protocol is used that includes informed consent from vaccinees and postvaccination antibody testing to detect nonresponders, who would then be eligible for revaccination (1).

In general, plasma-derived hepatitis B vaccine has induced seroconversion in similar proportions of vaccinees when vaccine has been administered by the IM and ID routes (5). However, immune responses to recombinant vaccine have not been equivalent after IM and ID vaccination. At least four studies have directly compared the immunogenicity of 1.0-mL doses of recombinant vaccine administered by the IM route to 0.1-mL doses administered by the ID route; in three of these, a greater proportion of vaccinees were protected after three IM doses (94%-97%) than after three ID doses (55%-78%) (6-8). In one study, the immune response was equivalent in both the IM and ID groups (9); however, the gender composition of these groups differed.

Age- and sex-specific variations in immune response may partially account for the poor immune responses to ID vaccination programs described in this report. In previous studies of recombinant vaccine, a smaller proportion of men (64%-71%) than women (87%-92%) responded to ID vaccination (6,10); in addition, both IM and ID vaccination routes induce better immune responses in younger vaccinees (10). Because of the generally poor immune response to ID vaccination and the demographic composition of public safety workers (e.g., some groups may consist predominantly of men, many of whom may be greater than 40 years of age), ID vaccination for public safety workers is not recommended. In comparison, the findings from Santa Barbara indicate that the recommended IM route of administration can induce excellent levels of protection against hepatitis B infection among public safety workers. In addition, the suitability of this approach was demonstrated by a program in Phoenix, Arizona, when in 1988 the Phoenix fire department vaccinated 820 male and 30 female employees with hepatitis B vaccine by the IM route (average age of vaccinees: 32 years). Of the 850 vaccinated persons, 803 (94%) developed protective levels of anti-HBs at a cost of $140 per employee, including postvaccination testing.

Because ID administration of hepatitis B vaccine induces a poor immune response, especially in older men, any potential savings in costs resulting from ID administration of the recommended vaccine dose will likely be negated by the costs of required postvaccination testing and additional vaccination of nonresponders. Assuming a full retail cost of $130 for three 1.0-mL doses of vaccine and a $10 cost for administration, the cost of IM vaccination is approximately $140 per vaccinee. Postvaccination antibody testing, which can add to the cost, should be considered for health-care workers at risk for percutaneous or permucosal exposure (1), although such testing may not be needed for others at lower occupational risk for hepatitis B.

ACIP has not recommended the ID administration of hepatitis B vaccine, and FDA has not licensed hepatitis B vaccine for ID administration. Moreover, ID vaccination programs offered by private contractors do not offer substantial cost savings over IM vaccination and may fail to induce immunity in a substantial proportion of vaccinees. For these reasons, vaccination programs should not use the ID route of administration.


  1. ACIP. Protection against viral hepatitis: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1990;39(no. RR-3):5-22.

2. Hadler SC. Hepatitis B virus infection and health care workers. Vaccine 1990;8(suppl):S24-8.

3. CDC. Guidelines for prevention of transmission of human immunodeficiency virus and hepatitis B virus to health-care and public-safety workers. MMWR 1989;38(no. S-6):9-10,12.

4. US Department of Labor, Occupational Safety and Health Administration. Occupational exposure to bloodborne pathogens: proposed rule and notice of hearing. Federal Register 1989;54:23042-139.

5. Zuckerman AJ. Appraisal of intradermal immunisation against hepatitis B. Lancet 1987;1:435-6.

6. Gonzales ML, Usandizaga M, Alomar P, et al. Intradermal and intramuscular route for vaccination against hepatitis B. Vaccine 1990;8:402-5.

7. Wistrom J, Settergren B, Gustafsson A, Juto P, Norrby RS. Intradermal vs. intramuscular hepatitis B vaccinations (Letter). JAMA 1990;264:181-2.

8. Bryan JP, Sjogren M, Iqbal M, et al. Comparative trial of low-dose, intradermal, recombinant- and plasma-derived hepatitis B vaccines. J Infect Dis 1990;162:789-93.

9. Parish DC, Muecke HW, Joiner TA, Pope WT, Hadler SC. Immunogenicity of low-dose intradermal recombinant DNA hepatitis B vaccine. South Med J 1991;84:387-94. 10. Morris CA, Oliver PR, Reynolds F, Selkon JB. Intradermal hepatitis B immunization with yeast-derived vaccine: serological response by sex and age. Epidemiol Infect 1989;103:402-5.

*For the private contractors used in reports 1-4, the specific laboratory testing methods and the definition of adequate antibody response are not known.

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