Rabies Despite Postexposure Prophylaxis in High-Burden Settings: Vaccine Failure or Gaps in Healthcare Delivery?

Abstract Background Rabies, a fatal zoonotic encephalitis, is preventable through timely postexposure prophylaxis (PEP), which includes wound care, vaccination, and local infiltration of immunoglobulins. However, reports of rabies despite PEP raise concerns about vaccine efficacy and protocol adherence. This study aimed to assess the burden and underlying causes of such apparent rabies “breakthrough” infections. Methods This retrospective study analyzed laboratory-confirmed rabies cases from 2018 to 2024 who had received PEP. Cases with at least 1 documented dose of rabies vaccine were included. “True” breakthrough infections (or PEP failures) were defined as rabies occurring despite initiation of PEP within 2 calendar days of exposure and documented completion of all required PEP components. Results Eighty-nine cases fulfilling the inclusion criteria were analyzed; only 3 were classified as “true” breakthrough infections. A majority of the cases were males (80.90%), and aged less than 15 years (64.04%). Exposure to dogs was reported in 93.26% cases, 80.9% were World Health Organization (WHO) Category III exposures, and 34.83% involved the head or neck. Postexposure prophylaxis was initiated within 2 days in 57.3% of cases; wound care was documented in 56.18%, vaccination completed in 46.07%, and only 26.39% of Category III cases received rabies immunoglobulins without any deviations. Conclusions The findings indicate that “true” breakthrough infections are uncommon, with most apparent PEP failures resulting from gaps in healthcare delivery. Such failures can undermine public confidence in vaccination, highlighting the need to strengthen awareness among healthcare workers and communities about the critical steps of PEP.