A 15‑year‑old who received subcutaneous rabies vaccine on day 0 and day 3 missed the scheduled third dose; how should the post‑exposure prophylaxis be completed?

Completing Rabies Post-Exposure Prophylaxis After a Missed Dose

Continue the vaccine series immediately without restarting—administer the missed third dose now and give the fourth dose 7 days after the original day 0, maintaining the standard 4-dose schedule on days 0,3,7, and 14. 1

Understanding Schedule Flexibility

The current rabies post-exposure prophylaxis regimen for previously unvaccinated individuals consists of 4 doses of vaccine administered intramuscularly on days 0,3,7, and 14, combined with human rabies immune globulin (HRIG) at 20 IU/kg on day 0. 1, 2

Delays of a few days for individual doses are unimportant and do not compromise protection. 1 The CDC explicitly states that most interruptions do not require restarting the entire series. 1 This is critical because:

• Virus-neutralizing antibodies typically peak by approximately day 14-28 after starting vaccination, meaning the protective immune response develops progressively throughout the series. 1
• HRIG provides immediate passive immunity at the wound site during the first 7-10 days before vaccine-induced antibodies develop, so the early doses (days 0 and 3) are the most crucial. 1
• Over 1,000 persons annually in the United States receive only 3 or 4 doses instead of the complete regimen, with no documented cases of rabies developing, even when >30% had confirmed exposure to rabid animals. 1

Specific Management for This Case

Since this 15-year-old received doses on day 0 and day 3 but missed the scheduled day 7 dose:

1. Administer the third dose immediately upon recognition of the missed appointment. 1
2. Schedule the fourth dose for day 14 (counting from the original day 0, not from today). 1
3. Do not restart the series—the first two doses have already primed the immune system. 1

Critical Considerations

Subcutaneous Route Issue

The vaccine was administered subcutaneously, which is incorrect. 1, 3 The standard route is intramuscular in the deltoid muscle for adolescents and adults. 1, 3 The gluteal area should never be used as it produces inadequate antibody response. 1, 3

• For the remaining doses, switch to the correct intramuscular route in the deltoid. 1
• The subcutaneous doses already given may have reduced immunogenicity, though this is not well-studied with modern cell-culture vaccines. 1

When to Consider Serologic Testing

For substantial deviations (delays of weeks or more), immune status should be assessed by serologic testing 7-14 days after the final dose. 1 However, for delays of only a few days, this is unnecessary. 1

Special Populations

If this patient is immunocompromised (taking corticosteroids, other immunosuppressive agents, has HIV, or other immunosuppressive illness), they require:

• A 5-dose regimen on days 0,3,7,14, and 28 (not the standard 4-dose schedule). 1, 4
• Mandatory serologic testing 1-2 weeks after the final dose to confirm adequate antibody response (≥1:5 serum dilution by RFFIT). 1, 4

Common Pitfalls to Avoid

• Do not restart the series from day 0—this wastes vaccine and delays completion of prophylaxis. 1
• Do not withhold the remaining doses thinking the series is "ruined"—even incomplete series have prevented rabies in exposed individuals. 1
• Do not administer additional HRIG at this point—it should only be given up to and including day 7 after the first vaccine dose. 1, 3
• Ensure future doses are given intramuscularly in the deltoid, not subcutaneously. 1, 3

Reassurance

The rabies incubation period typically ranges from 1-3 months (median ~35 days in the United States), providing a substantial window for immune response development. 1 When the recommended PEP regimen is completed, it is nearly 100% effective at preventing clinical rabies. 1, 4 No human rabies cases in the United States have been linked to incomplete or abbreviated rabies vaccine courses since the adoption of cell-culture vaccines. 1