Vetnews | September 2024 10 « BACK TO CONTENTS Rabies Vaccine for Prophylaxis and Treatment of Rabies: A Narrative Review Alan D. Kaye1 , Dominique M. Perilloux2 , Elizabeth Field2 , Cody A. Orvin2 , Spencer C. Zaheri2 , William C. Upshaw2 , Raju Behara1 , Tomasina Q. Parker-Actlis1, Adam M. Kaye3 , Shahab Ahmadzadeh1 , Sahar Shekoohi1, Giustino Varrassi4 1. Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA 2. School of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA 3. Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences University of the Pacific, Stockton, USA 4. Pain Medicine, Paolo Procacci Foundation, Rome, ITA Corresponding author: Sahar Shekoohi, sahar.shekoohi@lsuhs.edu Abstract Rabies, a millennia-old viral infection transmitted through animal bites, poses a lethal threat to humans, with a historic fatality rate of 100% if left untreated. Louis Pasteur’s introduction of the rabies vaccine in 1885 marked a turning point in the battle against rabies, preventing numerous cases. The purpose of this paper is to review the historical development, current challenges, and future prospects of rabies vaccination and treatment, with emphasis on the importance of continued research and collaborative efforts in the quest to eradicate this deadly infection. Historical vaccine development progressed from inactivated to live attenuated forms, with modern recombinant techniques showing promise. The preventive measures at present primarily involve vaccination, but challenges persist, such as differing safety profiles and immunogenicity among vaccine types. Pre-exposure prophylaxis with a three-dose vaccine series is crucial, especially in high-risk scenarios. Post-exposure prophylaxis combines human rabies immunoglobulin and inactivated rabies virus vaccine. The quest for the next generation of vaccines explores genetically modified and viral vector-based approaches; emerging treatments include gene therapy, virus-like particles, and monoclonal antibodies, offering hope for improved outcomes. Economic barriers to post-exposure prophylaxis, limited education, and awareness challenge rabies control. Cost-effective solutions and comprehensive awareness campaigns are vital for the successful eradication of rabies. More research and collaborative endeavours remain pivotal in the ongoing journey to eradicate rabies, one of the deadliest infectious diseases known to humans, if not met with prophylactic measures. Introduction And Background Rabies is a lethal viral infection often transmitted through animal bites or saliva entering through mucosal membranes or broken skin and has been known for thousands of years. It is caused by the bullet-shaped, single-stranded, negative-sense RNA Rhabdoviridae family of viruses, which are carried by both wild and domesticated animals. A viral envelope and ribonucleocapsid core contribute to viral virulence and cause nervous system infection, leading to severe symptoms like hydrophobia and aerophobia. Hydrophobia is defined as a fear of water, but for patients experiencing this symptom of rabies, it describes the fear of pain upon swallowing fluids. The pain is caused by spasms of the pharynx due to furious rabies infection, which is characteristic of 80% of human rabies infections. The remaining 20% of cases are paralytic. The presenting symptoms include fever, headache, and fatigue that progress to encephalomyelitis characterized by delirium. The five stages of the disease course are incubation, which can last from days to years; prodrome; acute neurologic illness; coma; and death, thought to be due to the massive inflammatory response in the central nervous system (CNS). Historically, rabies infection was 100% fatal, leading to increased suicide rates in individuals who believed they had contracted the disease. Thanks to Louis Pasteur developing the rabies vaccine in 1885, countless cases have been prevented, especially in developed countries [1]. Vaccination remains the foundation for preventing the infection that causes this viral zoonotic disease in exposed individuals. Along with vaccination, post-exposure prophylaxis includes wound cleaning and rabies immunoglobulin administration. Several types of rabies vaccines are available and utilized today. The issue with the numerous rabies vaccines that have been created is the vaccine candidate’s differing safety profiles and immunogenicity. Thus, continued efforts towards rabies vaccine research have focused on improving upon these factors. The limitations of the live-attenuated vaccine include inducing rabies in animals due to mutations in the host and resistant viral capabilities to cause infection [2]. The drawbacks of inactivated vaccines include lower immunogenicity, higher cost, and the requirement of multiple vaccinations during pre- and post-exposure to the rabies virus, which led to the development of adjuvanted vaccines [3]. Research efforts are now geared toward next-generation vaccines, like genetically modified and viral vector-based vaccines, which have limitations, including safety and proper distribution [2]. Preventative measures outside human vaccination include animal vaccination and spreading public awareness [1]. In 2018, the Global Strategic Plan was put in place by international organizations, including the World Health Organization, to eradicate human fatalities due to rabid canines by 2030, highlighting the importance of animal vaccination [2]. Targeted communities for rabies prevention education include high-risk populations like farmers and those who live in areas where rabies is endemic. Additionally, high-risk occupations, such as veterinarians, zookeepers, and forest workers, can receive pre-exposure prophylaxis [4]. This review will discuss the historical development, significance, and challenges surrounding rabies vaccines for prevention and treatment. Review Historical development of rabies vaccines Beginning as early as the first century BC, various techniques to treat rabies were practised [2]. 2024 Kaye et al. Cureus 16(6): e62429. DOI 10.7759/cureus.62429
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