Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017-2019)

Travel Med Infect Dis. 2024 Mar-Apr:58:102697. doi: 10.1016/j.tmaid.2024.102697. Epub 2024 Feb 17.


Background: Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure.

Method: The study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose.

Results: Age emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45-60 and 75-92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG.

Conclusions: This study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.

Keywords: Essen regimen; Post-exposure prophylaxis; Rabies; Rabies virus-neutralizing antibodies; Seroconversion.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Animals
  • Antibodies, Viral
  • Humans
  • Post-Exposure Prophylaxis
  • Rabies Vaccines*
  • Rabies virus*
  • Rabies* / epidemiology
  • Rabies* / prevention & control
  • Serbia / epidemiology


  • Antibodies, Viral
  • Rabies Vaccines