Rabies virus, as a neurotropic agent, is transmitted to humans usually after animal biting. Rabies is endemic in most Middle Eastern countries. Pre-exposure Prophylaxis (PrEP) program is recommended for high-risk populations in endemic areas. The present study reported 7 deaths from rabies infection despite human Post-Exposure Prophylaxis (PEP) and the evolution of their possible etiologies from 2014 to 2018 in Iran. In this study, 29 rabid human deaths were evaluated despite PEP in 2014-2018. Seven people deceased despite receiving PEP. The most damaged organs were hands and face (71.43%). Injecting anti-Rabies Immunoglobulin (RIG) around the wound, improper cleansing, and delayed PEP were the main causes of PEP failure. In addition, immunodeficiency in a patient was another cause of failure. Our obtained data suggested that immediate precise measures after exposure based on the World Health Organization (WHO) recommendation, maintaining the temperature integrity (cold chain) of vaccines, and RIGs during transportation, and performing detailed injection schedule could prevent PEP failure in most cases. Furthermore, society’s awareness plays a key role in controlling the disease, especially in endemic areas.
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