Historical Rabies Vaccination: Abdominal Multiple-Dose Regimens
The Historical Practice
Multiple small-volume rabdominal injections of rabies vaccine were administered historically because early nerve tissue-based vaccines required 14–21 daily doses given subcutaneously in the abdominal wall, a practice that persisted from Pasteur's era (1885) through the mid-20th century until modern cell culture vaccines replaced them. 1, 2, 3
Why the Abdomen Was Used
Large surface area for multiple injection sites – The abdominal wall provided sufficient space to rotate injection sites over the prolonged 2–3 week course, minimizing local tissue reactions at any single site. 4
Subcutaneous tissue accessibility – Early nerve tissue vaccines were administered subcutaneously (not intramuscularly), and the abdomen offered easily accessible subcutaneous tissue with minimal risk of inadvertent intramuscular injection. 4
Avoidance of more painful sites – Compared to limbs, the abdominal wall was perceived as less painful for the daily injections required by these crude vaccine formulations. 4
Why Multiple Doses Were Necessary
Low immunogenicity of nerve tissue vaccines – Pasteur's original rabies vaccine and subsequent nerve tissue-based products contained inactivated virus grown in animal spinal cord or brain tissue, yielding very low viral antigen concentrations that required 14–21 consecutive daily doses to generate protective antibody levels. 1, 2, 3
Lack of adjuvants and purification – These early vaccines lacked modern adjuvants and purification techniques, necessitating repeated antigen exposure to achieve seroconversion. 1, 3
When This Practice Was Abandoned
Transition to cell culture vaccines (1960s–1980s) – The development of human diploid cell vaccine (HDCV) and other tissue culture-based vaccines in the 1960s–1980s dramatically improved immunogenicity and safety, allowing reduction from 14–21 doses to the modern 4–5 dose intramuscular regimens. 1, 2, 3
Modern administration sites – Current CDC and WHO guidelines mandate intramuscular injection in the deltoid (adults/older children) or anterolateral thigh (young children), never the abdomen or gluteal area, because intramuscular administration in these specific sites ensures optimal immune response. 4, 5, 6
Elimination of subcutaneous route – Modern cell culture vaccines (HDCV, PCECV) are administered intramuscularly at 1.0 mL per dose on days 0,3,7, and 14, combined with rabies immune globulin (20 IU/kg) infiltrated into wounds on day 0. 4, 5, 7
Critical Safety Concerns with Historical Nerve Tissue Vaccines
High rates of neurological complications – Nerve tissue vaccines carried a risk of post-vaccinal encephalomyelitis and other serious neurological adverse events due to myelin contamination, a problem entirely eliminated by modern cell culture vaccines. 1, 2, 3
Variable potency and efficacy – The crude production methods resulted in inconsistent viral antigen content and unpredictable immune responses, contributing to prophylaxis failures. 1, 3
Modern Intradermal Regimens (Not Abdominal)
Cost-reduction strategies in resource-limited settings – Some international protocols use intradermal administration of 0.1 mL doses at multiple sites (deltoid, suprascapular, thigh) on days 0,3,7, with boosters on days 28 and 90, but these are given in the limbs and upper body—never the abdomen—to reduce vaccine volume and cost while maintaining immunogenicity. 4, 8, 1
Not FDA-approved in the United States – These intradermal multi-site regimens are used abroad but have not been submitted for FDA approval; U.S. protocols require standard 1.0 mL intramuscular doses in the deltoid or thigh only. 4