Post-exposure prophylaxis and possible breakthrough infections among human rabies case in China, 2019–2024: a nationwide retrospective surveillance study

Background Rabies remains a uniformly fatal yet preventable zoonotic disease that continues to pose a public health threat in China, especially in rural populations. Although post-exposure prophylaxis (PEP) is highly effective when delivered promptly and correctly, deaths still occur, including rare infections that develop despite prophylaxis. This study characterized exposure patterns, PEP use, and possible breakthrough infections among human rabies deaths in China from 2019 to 2024. Methods We conducted a retrospective cross-sectional analysis of data from China's national rabies surveillance system. Clinically diagnosed and laboratory-confirmed human rabies cases reported between 1 January 2019 and 31 December 2024 were included. We analyzed demographic characteristics, exposure information, animal sources, wound sites, PEP measures, and incubation periods. Multivariable unconditional logistic regression identified factors associated with PEP receipt, while Cox proportional hazards models, Mann–Whitney U tests, and Kruskal–Wallis H tests were used to examine factors associated with the incubation period. Chi-square or Fisher's exact tests compared standard and non-standard PEP cases. Results Among 930 human rabies deaths, most patients were male, rural farmers, and middle-aged or older adults. Dogs caused 86.88% of exposures, yet only 1.83% of owned biting animals had documented rabies vaccination. PEP uptake was very low: 852 cases (91.62%) received no prophylaxis whatsoever, and only 51 cases (5.48%) received rabies vaccine. Non-category III exposure, wounds at lower-risk sites, injury by household animals, and single-victim incidents were associated with lower likelihood of receiving wound care, vaccination, or rabies immunoglobulin. Among 697 cases with a documented incubation period, the median was 70 days (IQR: 38–134.5). Head, face, or neck exposure and multiple-victim incidents were independently associated with shorter incubation periods. Seventy-eight patients developed rabies despite receiving at least one prophylaxis measure; 60 (76.92%) had clearly non-standard PEP, whereas 18 (23.08%) had no identifiable procedural failure. These possible breakthrough infections accounted for 1.94% of all cases and were characterized by category III exposure, head, face, or neck injuries, stray-dog bites, and a short median incubation period of 16 days. Conclusion Most human rabies deaths in China resulted from a failure to initiate or complete PEP, reflecting preventable gaps in risk perception, access, affordability, and follow-up. Possible breakthrough infections were rare but were concentrated in extremely high-risk exposures. Targeted health education, improved prophylaxis adherence, integrated bite case management, and strengthened dog vaccination under a One Health framework are essential to eliminate dog-mediated human rabies deaths.