Hepatitis B vaccine is traditionally administered intramuscularly, using a needle of 1.0 to 1.5 inches in length and 20- to 25-gauge in caliber. The preferred injection site is the deltoid muscle in adults and anterolateral thigh muscle in infants. Among 194 health care workers who received intramuscular buttock injections of hepatitis B vaccination, only 58% subsequently developed detectable anti-HBs titers . This finding was verified by a prospective randomized trial where health care workers who received immunization in the arm achieved higher seroconversion rate of 93% and GMT of 1454 mlU/mL, as compared with those who were injected in the buttock. Among those who received buttock injection, the seroconversion rate (83% versus 72%) and the GMT (387 mlU/mL versus 85 mlU/mL) were higher with the use of 2-inch needles versus 1-inch needles . Buttock injection makes intramuscular delivery of the vaccine difficult and should be avoided.
Intradermal injection of vaccine leads to very efficient antigen processing. It requires only 10% of the dose used conventionally for intramuscular injection and thus might offer a cost-effective advantage. However, data regarding the immunogenicity of intradermal vaccination, compared with the intramuscular route, remain controversial, and the long-term immuno-gencity of intradermal vaccine remains to be established . Among 425 health care workers randomized to receive plasma-derived hepatitis B vaccines at doses of 2 mcg intradermally or 20 mcg intramuscularly, postvaccination GMT was significantly lower in the intradermal group . In a group of hospital employees who were retested 2 years after a documented response to primary HBV vaccination, more subjects who had received intramuscular inoculations as compared with those who received it by the intradermal route maintained durable response (89% versus 64%), with GMT of 66.4 mIU/mL and 20.7 mIU/mL, respectively . In a study using an accelerated scheme of hepatitis B vaccine over a 6-week period for postexposure prophylaxis, anti-HBs seroconversion was achieved in significantly more patients who underwent the intramuscular than intradermal route (77% versus 45%). The investigators in this latter report discouraged the use of an accelerated low-dose intradermal schedule when rapid protection against HBV was desired .
In contrast, other clinical studies of intradermal hepatitis B vaccine reported some encouraging results in subjects who were nonimmunized as well as previous nonresponders to intramuscular immunization . A trial of 50 health care workers who were randomized to receive either intramuscular or intradermal vaccine series yielded comparable seroconversion rates of 100% and 96%, respectively . In another study of 1400 health care workers, protective anti-HBs titer was achieved in only 68% of subjects after the third intradermal dose of hepatitis B vaccine, but an additional dose of 2 mcg by the same route increased those with adequate protective titer to 89% . Four doses of 2-mcg intradermal vaccines would still cost significantly less than three doses of 20-mcg intramuscular shots. Intradermal vaccine was also explored for use as a booster injection in individuals whose anti-HBs decreased to below 10 mlU/mL 3 years after the primary vaccination series. It was equally effective as an intramuscular booster injection in inducing an antibody response but was associated with more frequent local reactions, such as pain and discoloration at the injection site (42% versus 17%) .
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