Intradermal Rabies PEP for Previously Vaccinated Patients in Endemic Settings
Yes, the intradermal (ID) regimen using the Thai Red Cross schedule is equally acceptable and guideline-approved by WHO and ACIP for previously vaccinated individuals requiring rabies PEP, though the FDA-approved protocol in the United States remains the IM regimen. 1
Regulatory Recognition and Context
Both WHO and ACIP explicitly recognize the Thai Red Cross intradermal schedule as an efficacious alternative to the intramuscular regimen for previously vaccinated individuals. 1 The key distinction is:
- IM Regimen (CDC/ACIP/FDA-approved): 2 doses of 1.0 mL IM in the deltoid muscle on days 0 and 3, without rabies immunoglobulin 1, 2
- ID Regimen (WHO/Thai Red Cross): 0.1 mL ID doses at two sites on days 0,3, and 7, followed by single 0.1 mL boosters on days 30 and 90 1
The ID schedules have not been submitted for FDA approval in the United States but are recognized as effective alternatives in rabies-endemic countries like Thailand. 1
Evidence Supporting ID Equivalence
The ID regimen demonstrates equivalent immunogenicity to IM administration for previously vaccinated individuals:
- A 2023 comparative study showed that all participants developed adequate neutralizing antibodies (≥0.5 IU/mL) by day 28, regardless of whether they received ID or IM PEP, with similar T cell responses and antibody titers between both regimens 3
- Cross-over studies demonstrate that switching between IM and ID routes for booster vaccination produces equivalent 15-fold rises in rabies virus neutralizing antibody response with no difference in anamnestic immune response 4
- Four-site single-day ID booster regimens produce significantly higher antibody responses (two- to eightfold) compared to conventional two-dose IM regimens at multiple time points 5
Practical Advantages of ID Regimen
The ID regimen offers substantial benefits in endemic settings without compromising protection:
- Uses 1/10th the vaccine volume of IM regimen, providing significant cost savings 1
- A 2024 study confirmed that even a single ID booster dose is sufficient for producing adequate antibody levels in >95% of participants and enhances antibody avidity maturation 6
- The 1-week ID Institut Pasteur Cambodge regimen is as effective as the 2-week IM 4-dose Essen regimen under real-life PEP conditions 3
Critical Administration Requirements
Regardless of route chosen, certain principles must be followed:
- Never administer vaccine in the gluteal area, as this produces inadequate antibody responses 1, 2
- For adults: deltoid muscle (IM) or deltoid area (ID); for young children: anterolateral thigh 1, 2
- Previously vaccinated individuals should NOT receive rabies immunoglobulin, as it inhibits the anamnestic immune response 1, 2
Special Population Considerations
Immunocompromised patients require different management:
- Immunosuppressed individuals should receive the full 5-dose vaccine regimen (days 0,3,7,14, and 28) plus HRIG at 20 IU/kg, even if previously vaccinated 2, 7
- Serologic testing is mandatory 7-14 days after completion to confirm adequate antibody response 2, 7
- Conditions causing immunosuppression include corticosteroid use, other immunosuppressive medications, antimalarials, HIV/AIDS, and other immunosuppressive illnesses 2
Clarification for Your Practice Setting
For previously vaccinated patients in Thailand or other endemic regions using WHO-approved protocols, the ID regimen (Thai Red Cross schedule) is fully acceptable and guideline-endorsed. 1 The IM regimen referenced in standard CDC/ACIP guidance reflects FDA-approved protocols for the United States, but this does not diminish the validity of WHO-endorsed ID regimens for your practice context. Both approaches are evidence-based and effective for previously vaccinated individuals requiring PEP. 1, 3