For a previously vaccinated patient re-exposed to rabies, is the intradermal (ID) regimen (using the Thai Red Cross schedule) equally acceptable and guideline-approved as the intramuscular (IM) regimen for post-exposure prophylaxis (PEP) and boosters?

Intradermal vs Intramuscular Rabies PEP for Previously Vaccinated Patients

For previously vaccinated patients re-exposed to rabies, the intradermal (ID) regimen using the Thai Red Cross schedule is equally acceptable and guideline-approved as the intramuscular (IM) regimen, though the IM regimen remains the FDA-approved standard in the United States while ID regimens are explicitly recognized by WHO and ACIP as efficacious alternatives used internationally. 1

Understanding the Regulatory Context

US (CDC/ACIP) Guidelines: IM Standard

• The CDC/ACIP recommends 2 doses of 1.0 mL IM (deltoid) on days 0 and 3 for previously vaccinated individuals, without rabies immunoglobulin. 1, 2, 3
• This IM regimen is the FDA-approved protocol for use within the United States. 1
• Previously vaccinated persons are defined as those who completed a recommended pre-exposure or post-exposure series with cell-culture vaccines (HDCV, PCECV, or RVA) or have documented adequate antibody response. 1, 2

International Guidelines: ID Regimens Explicitly Recognized

• ACIP explicitly acknowledges that ID regimens are "efficacious among persons bitten by rabid animals" and are "widely used" internationally, particularly the Thai Red Cross schedule. 1
• The Thai Red Cross (2-2-2-0-1-1) regimen uses 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
• These ID schedules have not been submitted for FDA approval in the United States but are recognized as effective alternatives in rabies-endemic countries. 1

Evidence Supporting ID Regimen Equivalence

Immunogenicity Data for Previously Vaccinated Persons

• Research demonstrates that ID booster vaccination produces robust anamnestic responses in previously vaccinated individuals, with antibody titers often exceeding those from IM boosters. 4, 5, 6
• A four-site ID booster regimen (given on day 0 alone) produced significantly higher neutralizing antibody titers (2- to 8-fold higher) than the conventional two-dose IM regimen in previously vaccinated individuals. 6
• Crossing over between IM and ID routes for booster vaccination produces equivalent 15-fold rises in neutralizing antibodies with no difference in safety or efficacy. 5

Real-World Effectiveness

• A 2023 comparative study demonstrated that the ID 2-site, 3-visit regimen achieved 100% seroconversion (≥0.5 IU/mL) at day 28, identical to the IM 4-dose regimen, with similar T-cell responses and neutralizing antibody titers. 7
• Recent data from Thailand shows that a single ID booster dose (0.1 mL) produces adequate antibody levels in >95% of participants with enhanced antibody avidity maturation. 8

Practical Guidance for Your Setting

When to Use ID vs IM

For previously vaccinated patients in rabies-endemic regions using national ID programs:

• The Thai Red Cross ID schedule is guideline-approved by WHO and explicitly recognized as efficacious by ACIP for previously vaccinated individuals. 1
• The ID regimen offers significant cost savings (using 1/10th the vaccine volume) without compromising protection. 1
• For previously vaccinated persons specifically, even simplified ID regimens (such as 2 doses of 0.1 mL at 2 sites on days 0 and 3) produce robust anamnestic responses. 4, 5

For patients in the United States or using US protocols:

• The IM regimen (1.0 mL deltoid on days 0 and 3) remains the FDA-approved standard. 1, 2
• This is the legally defensible approach in US medical-legal contexts. 1

Critical Caveats

Immunocompromised patients require special consideration:

• Immunosuppressed individuals should receive the full 5-dose IM series (days 0,3,7,14,28) plus HRIG, regardless of previous vaccination status, with mandatory serologic testing to confirm adequate response. 3, 9
• Conditions causing immunosuppression include corticosteroid use, HIV/AIDS, antimalarials, and other immunosuppressive medications or illnesses. 3

Administration technique matters:

• Vaccine must never be administered in the gluteal area, as this produces inadequate antibody responses. 1, 3
• For adults: deltoid muscle (IM) or deltoid area (ID). 1
• For young children: anterolateral thigh is acceptable. 1

HRIG is contraindicated in previously vaccinated persons:

• Previously vaccinated individuals should NOT receive rabies immunoglobulin, as it inhibits the anamnestic immune response. 2, 3, 9

Bottom Line for Your Practice

If you are practicing under WHO/national guidelines in a rabies-endemic country with an established ID program, the Thai Red Cross ID schedule is fully appropriate and guideline-supported for previously vaccinated patients. 1 The evidence demonstrates equivalent or superior immunogenicity compared to IM regimens for this population. 5, 6, 7

If you are practicing in the United States or need to document FDA-approved protocols, use the IM regimen (1.0 mL deltoid days 0 and 3). 1, 2

Both approaches are scientifically sound for previously vaccinated, immunocompetent individuals—the choice depends on your regulatory context, vaccine availability, and cost considerations. 1