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Clin Infect Dis. 2006 Feb 15;42(4):e16-20. Epub 2006 Jan 10.

Clinical and immunological comparison of smallpox vaccine administered to the outer versus the inner upper arms of vaccinia-naive adults.

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  • 1Department of Medicine, Dwight D. Eisenhower Army Medical Center, Fort Gordon, GA 30905-5650, USA.



Current recommendations direct health care providers to administer smallpox vaccine to the upper outer arm. However, concerns about cosmetically bothersome scarring, accidental contact transmission, interference by body tattoos, and even malignant transformation suggest evaluation of alternate vaccination sites is warranted.


We randomized 20 vaccinia-naive adults to undergo smallpox vaccination on the outer (n = 10) or inner (n = 10) upper arm. Evaluations included major reaction ("take") rates and vaccination site cultures on postvaccination day 7, determination of serum vaccinia-specific neutralizing antibody titers on days 0 (prevaccination) and 21, and determination of adverse events.


On postvaccination day 7, a total of 18 participants (9 per group) had major reactions, 17 of whom had culture evidence of viable vaccinia. The inner and outer arm groups had similar major reaction mean sizes (P = .17), but the amount of erythema (in square centimeters) was smaller in the inner arm group (P = .05). At day 21, all participants had higher titers of vaccinia-specific neutralizing antibodies, compared with at day 0, and the geometric mean titer values of the 2 vaccine groups were similar (P = .45). Adverse event rates were similar.


The comparable clinical, immunological, and tolerability outcomes between smallpox vaccine applied to the conventional upper outer arm site versus the upper inner arm, coupled with modestly less vaccine-site erythema on the inner arm, indicate that the inner arm may be a suitable alternate vaccination site.

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