Measuring antibody titres following rabies postexposure prophylaxis in immunosuppressed patients: a norm rather than the exception

We present a case of a 51-year-old immunosuppressed man with underlying chronic lymphoproliferative leukaemia (CLL), who presented to us in emergency with breathlessness, hydrophobia, anxiety and restlessness. He had a history of category 3 dog bite 2 months ago and had received a full course of rabies immunoglobulin and antirabies vaccine (ARV) as per the national schedule. As there were frank clinical reports of rabies, the patient was managed according to Milwaukee regimen. The patients died within a week of the appearance of symptoms. The brain autopsy revealed Negri bodies conforming the mortality due to rabies.Immunosuppressed patients, like our patient who had CLL have low antibody formation after rabies prophylaxis. Antibody titres in immunosuppressed patients need to be measured after the 2–4 weeks of the last injection of ARV to decide whether a booster of ARV needs to be administered or not.

Evaluating Surveillance for and Estimating Administration of Rabies Postexposure Prophylaxis in the United States, 2012–2018

Background An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. Methodology/Principle findings To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012–2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012–2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. Conclusions Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment.

Non-Vertical Exposures to HIV, HBV and HCV Infection in Children and Adolescents—Risk of Infection, Standards of Care and Postexposure Prophylaxis

Introduction: in the review, we aimed to present current knowledge about the risk of infection, standards of care, and postexposure prophylaxis (PEP) in pediatric patients after non-vertical exposures to HIV, HBV, and HCV infection. Materials and Methods: the latest available literature and recommendations of Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), European recommendations for the management of HIV and administration of non-occupational PEP, and Polish AIDS Society were reviewed. Results: the majority of cases of non-vertical exposure to blood-borne viruses in the pediatric population consist of sexual exposition and injection with unsterilized sharp objects (usually needlestick injuries). The risk HIV, HBV, and HCV transmission depend on several factors, and each exposure should be evaluated individually with consideration of the patient’s medical history. It is crucial to start antiretroviral therapy within 48 h from exposure. Treatment is continued for 28 days, and a 3-drugs regiment is recommended in the majority of cases. Decisions on hepatitis B and tetanus PEP are based on a history of vaccination. There is no PEP for hepatitis C infection, follow-up testing aims for early identification of disease and consideration of treatment options. Conclusion: all children after the non-vertical exposure to HIV, HBV, and HCV infection should be evaluated by the Infectious Disease specialist as soon as possible after the incident and qualified to post-exposure prophylaxis. Systematic diagnostic and follow-up on children after significant needlestick exposure should be maintained. Children after sexual exposure need a multidisciplinary approach. Response to reported event must be rapid and treatment must be comprehensive.

Preexposure and Postexposure Prophylaxis of Rabies With Adeno-Associated Virus Expressing Virus-Neutralizing Antibody in Rodent Models

Rabies, a fatal disease in humans and other mammals, is caused by the rabies virus (RABV), and it poses a public health threat in many parts of the world. Once symptoms of rabies appear, the mortality is near 100%. There is currently no effective treatment for rabies. In our study, two human-derived RABV-neutralizing antibodies (RVNA), CR57 and CR4098, were cloned into adeno-associated virus (AAV) vectors, and recombinant AAVs expressing RVNA were evaluated for postexposure prophylaxis after intrathecal injection into RABV-infected rats. At 4days post-infection with a lethal dose of RABV, 60% of the rats that received an intrathecal injection of AAV-CR57 survived, while 100% of the rats inoculated with AAV-enhanced green fluorescent protein (EGFP) succumbed to rabies. Overall, these results demonstrate that AAV-encoding RVNA can be utilized as a potential human rabies postexposure prophylaxis.