Administration Of Post-exposure Prophylaxis Research Articles

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission

BackgroundLeprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP.MethodsThe PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome.DiscussionPast studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities.Trial registrationNL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060

Prevalence of delayed initiation of rabies postexposure prophylaxis and factors influencing it among animal bite victims from Eastern Uttar Pradesh, India.

In a rabies-endemic country like India, every animal bite is potentially taken as rabid exposure and timely and appropriate postexposure prophylaxis (PEP) is crucial as rabies is an almost 100% fatal disease. A retrospective record-based study was conducted at an anti-rabies clinic (ARC) in Eastern Uttar Pradesh, India. Data of the animal bite victims attending the ARC for PEP from January to December 2022 were extracted from the records. A semistructured questionnaire was used for collecting information regarding the interval between exposure and the initiation of anti-rabies PEP, age, gender, residence, the bite site on the body, category of exposure and other risk factors associated with the delay in PEP. Most of the victims were male (67.6%), from an urban background (61.3%) and aged up to 20 y (43.9%). Out of the 222 victims, 62 (27.9%) had delayed initiation of PEP (>48 h after exposure). Factors found to be significantly associated with delayed initiation of PEP were residence (p=0.01), age (p=0.04) and the type of biting animal (p=0.002). Delayed initiation of PEP is common among animal bite victims in this region of India, although PEP is affordable. Educational programmes and awareness-raising campaigns for timely administration of PEP should be a priority, especially targeting rural residents, those aged<18 y and those bitten by animals other than dogs.

Risk Reduction Strategies for Rabies Exposures and Prophylaxis in Children

Annually, 59,000 people die of rabies, the world’s oldest known infectious disease, globally. In the United States, canine rabies has been virtually eliminated but the risk of rabies due to wildlife, especially raccoons, skunks, and bats, has required post exposure prophylaxis (PEP) be administered to more than 60,000 patients annually1. In 2021, 5 people in the United States2 died of rabies mostly due to misinformation or improper treatment. Rabies post exposure prophylaxis consists of three steps, wound washing, administration of human rabies immune globulin (HRIG) and a full course of vaccine3. In 2022, Whitehouse4 published that there were 122 breakthrough rabies infections when PEP was given due to four factors: 1) deviations from core practice 2) delays in seeking health care 3) errors in administration of HRIG 4) comorbidities or immunosuppression. It is estimated that over 40% of PEP administration is given inappropriately. The publication,” Safety, and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure”, Human Vaccines &amp; Immunotherapeutics, 17:7, 2090–20965, was the first study that prospectively reviewed the use of human rabies immune globulin 150 IU/ml in 30 pediatric patients ages 0.5–14.9 years old. Globally, 40% of people bitten by animals suspected of being infected with the rabies virus are children under the age of 15.6 This paper will look at risk reduction strategies that will include: Proper Identification of major rabies vectors Special risks associated with bat exposures in children Administration of human rabies immune globulin with volume considerations in children Special administration consideration for rabies vaccines “Just -in- time “Education for health care providers Illustrative cases will be used to demonstrate each of these strategies of risk as well as the strategies for risk reduction.

Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May–July 2022

BackgroundMay 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. MethodsHigh-risk contacts identified during 20 May–22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. ResultsTwo-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. ConclusionsPEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

Active safety surveillance of rabies monoclonal antibody and rabies vaccine in patients with category III potential rabies exposure.

A vero cell-based inactivated Rabies Vaccine (Rabivax-S) and Rabies Human Monoclonal Antibody (Rabishield) have been approved since 2016. A post-marketing surveillance was conducted in India from 2020 to 2021 to gather real world safety data on Rabivax-S and Rabishield. This was non-interventional active surveillance in patients with category III potential rabies exposure who were administered a post-exposure prophylaxis (PEP) regimen (Rabishield and Rabivax-S) by their healthcare providers (HCPs) as per the dosages and regimens mentioned in the package insert approved by the Indian regulators. The approved schedule for PEP was local infiltration of Rabishield on Day 0 and five doses of Rabivax-S on Day 0, 3, 7, 14, and 28 (Intramuscular route, IM) or four doses of Rabivax-S on Day 0, 3, 7, and 28 (Intradermal route, ID). The primary objective of this surveillance was to generate real-world evidence on the safety and tolerability of Rabishield and Rabivax-S. All patients enrolled in the surveillance were required to report any adverse events (AEs) occurring up to Day 31 after initiation of PEP (administration of Rabishield and the first dose of Rabivax-S) to their HCP. A total of 1000 patients with category III potential rabies exposure were enrolled across India. 991 patients received the PEP regimen with IM Rabivax-S while 9 received a PEP regimen with the ID regimen. While 32% of the patients were <12 years of age, 11.8% were ≥12 to <18 years of age and 56.2% were ≥18 years of age. The entire PEP regimen was completed by 97.3% of the enrolled patients. A total of 69 AEs were reported in 64 patients. Out of these, 49 AEs in 47 patients were assessed as causally related to the study products (26 with Rabishield and 23 with Rabivax-S). The majority of the AEs were mild and all recovered without any sequelae. One serious adverse event (SAE) of fracture of the hand was reported which was not related to either Rabishield or Rabivax-S. No case of rabies was reported. Rabishield and Rabivax-S have an excellent safety profile and are well tolerated. No participant developed rabies during 31 day follow up. The PMS was funded by Serum institute of India Private Limited which is the manufacturer of the study products.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Using Integrated Bite Case Management to estimate the burden of rabies and evaluate surveillance in Oriental Mindoro, Philippines.

Despite national elimination efforts, dog-mediated rabies remains endemic in the Philippines. Free provision of post-exposure prophylaxis (PEP) through the widespread establishment of Animal Bite Treatment Centers (ABTCs) has improved accessibility; however, the resulting upsurge in PEP demand is not sustainable, and human rabies deaths continue. Dog vaccination coverage also remains inadequate, and it is unclear whether surveillance is effective. Here, we used Integrated Bite Case Management (IBCM) to collect enhanced rabies surveillance data in Oriental Mindoro Province over a 3-year period (2020-2022). Adapting a probabilistic decision tree model, we estimated the burden of rabies, evaluated surveillance performance, and analyzed the costs and benefits of current rabies prevention and control practices in the province. The incidence of bite patients receiving PEP was high in Oriental Mindoro Province (1,246/100,000 persons/year), though < 3% of presenting patients were deemed high-risk for rabies exposure (24/100,000 persons/year). Using a decision tree model, we estimated that around 73.8% of probable rabies-exposed patients sought PEP (95% Prediction Interval, PrI: 59.4%-81.1%) and that routine surveillance confirmed < 2% of circulating animal rabies cases, whereas IBCM resulted in a nearly fourfold increase in case detection. Furthermore, we estimated that an average of 560 (95% PrI 217-1,090) dogs may develop rabies annually in the province, equating to 3-5 cases per 1,000 dogs per year. On average, 20 to 43 human deaths were averted by PEP each year in Oriental Mindoro at an annual cost of $582,110 USD (i.e., $51.44 USD per person) or $20,190 USD (95% PrI $11,565-79,400) per death averted. While current practices for PEP provisioning in the Philippines have improved access, a large proportion of people exposed to rabies (> 26%, 95% PrI 18.8%-40.1%) are still not seeking healthcare. Integrating an intersectoral surveillance system, such as IBCM, into national policy could greatly improve case detection if well implemented, with further benefits extending to guidance for PEP administration, potentially reducing unnecessary expenditure on PEP, and situational awareness to inform control of rabies through mass dog vaccination.

Human Rabies — Texas, 2021

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom onset. Fifty-seven persons who met criteria for suspected or known exposure to infectious secretions in this case were advised to consult with a medical provider about the need for rabies PEP in accordance with Advisory Committee on Immunization Practices (ACIP) guidelines (1). Rabies, an acute, progressive neuroencephalitis, is nearly always fatal. Although dogs are the most common source of human rabies deaths worldwide and account for an estimated 59,000 annual cases of human rabies globally (2), bats are the most common source of domestically acquired rabies in the United States and have been implicated in 31 (81.6%) of 38 human infections since 2000 (3). Attempts to prevent death or poor neurologic outcomes once rabies symptoms develop have been largely unsuccessful (4). Administration of rabies PEP, comprising rabies immunoglobulin and a series of doses of rabies vaccine, is critical to preventing rabies after an exposure; enhanced public education about the risk posed by bats, and the availability of PEP to prevent rabies, is needed.

Rabies research in Ethiopia: A systematic review

Rabies is an important zoonosis in Ethiopia, where lack of research is cited as a constraint to implementation of the national rabies control strategy. We conducted a systematic review of publications and theses on rabies in Ethiopia, to document research gaps and areas of knowledge saturation in relation to geographic and species focus, methods and findings. We also examined funding sources and extent of local researcher participation. After screening titles and abstracts, the full text of 119 publications was included in data extraction. More than 40% of publications involved data collection in one region (Oromia); no publications reported findings from Benishangul-Gumuz, Dire Dawa or Gambella. Dogs and wildlife (especially Canis simensis) were the focus of research in 45% and 24% publications, respectively. Descriptive epidemiology (N = 39 publications), ethno-medicine/−pharmacology (N = 17) and knowledge, attitude, and practice surveys (KAP, N = 15) were amongst the most common study designs, while studies involving economic methods (N = 3) and experimental epidemiology to test interventions (N = 3) were under-represented. Incidence surveys (N = 9) commonly used post-exposure prophylaxis administration in humans as a proxy for exposure without laboratory confirmation of the rabies status of the animal. KAP surveys tended to highlight reasonable levels of knowledge of rabies and poor practices, including overreliance on medicinal plants. International researchers were the first or last (senior) author on 42% and 58% of publications, respectively, most of which were funded by international organizations (45/72 publications reporting funding source). Based on this systematic review, we suggest more applied research is needed to address gaps in laboratory surveillance (including in humans, domestic and wild animals); identify effective ways to overcome socio-cultural and other barriers to accessing effective rabies treatments; inform best approaches to incentivizing mass dog vaccination programs; and generate local estimates of the cost-benefit and cost-effectiveness of different control strategies to improve financing and political buy-in for rabies control in Ethiopia.

Applicability and benefits of telemedicine in the monitoring of monkeypox close contacts.

Monkeypox is a zoonotic disease caused by the monkeypox virus and classically presents as a vesicular rash accompanied by fever and lymphadenopathy. Singapore reported the first imported case of monkeypox infection on 21 June 2022, the first local unlinked case on 6 July 2022, and the first local linked case on 5 August 2022. Telemedicine was used in the management of monkeypox close contacts to (1) screen for the development of signs and symptoms consistent with monkeypox infection, (2) assess for successful post-exposure prophylaxis via direct visualisation of vaccination site morphological progression, (3) detect serious reactions arising from post-exposure prophylaxis administration, and (4) evaluate for deterioration in mental health status during the 21-day quarantine period. A case series of 13 close contacts who received post-exposure prophylaxis in the form of the ACAM2000 live Vaccinia virus preparation is presented, illustrating the safe and efficacious application of telemedicine in the clinical follow-up of quarantined close contacts throughout the 21-day incubation period, and post-exposure prophylaxis monitoring. Inherent limitations included difficulties in the assessment of sensitive areas such as the peri-genital and peri-anal regions and video quality-related issues.

Post-exposure prophylaxis to prevent varicella in immunocompromised children

SummaryBackgroundVaricella-zoster virus (VZV) infection can cause life-threatening events in immunocompromised patients. Post-exposure prophylaxis (PEP) is required to prevent secondary VZV infection. Limited evidence is available for the use of acyclovir (ACV)/valacyclovir (VCV) as PEP.MethodsHerein, we retrospectively analyzed immunocompromised paediatric patients with significant exposure to VZV. Patients administered PEP were categorized into four groups: 1) ACV/VCV group; 2) intravenous immunoglobulin (IVIG) group; 3) ACV/VCV/IVIG group; 4) vaccine group.ResultsAmong 69 exposure events, 107 patients were administered PEP (91, ACV/VCV; 16, ACV/VCV/IVIG) and 10 patients did not receive PEP (non-PEP group). The index case was diagnosed based on clinical symptoms in 55 cases (79.7%). Fourteen cases (20.3%) were confirmed using direct virological diagnostic procedures. In the PEP group, only 2 patients (2.2%) developed secondary VZV infections. Additionally, 2 patients in the non-PEP group (20.0%) developed secondary VZV infection. The incidence of secondary VZV infection was significantly lower in the PEP group than in the non-PEP group (P=0.036). Among patients administered PEP, no antiviral drug-induced side effects were detected.ConclusionsAntiviral agents administered as PEP are effective and safe for preventing VZV infections in immunocompromised patients. Rapid virological diagnosis of index cases might allow efficient administration of PEP after significant exposure to VZV infection.

Implementation of Clinical Decision Support on Emergency Department Delivery of Human Rabies Immune Globulin

Fatal human rabies infections can be prevented through appropriate rabies postexposure prophylaxis (PEP). Errors in patient selection and administration of human rabies immune globulin in the emergency department (ED) setting were identified in a previous study of rabies PEP administration. To test the a priori hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 human rabies immune globulin quality indicators compared with preimplementation controls. This quality improvement study was conducted in 15 EDs in a US multihospital health system. Patients who received human rabies immune globulin or rabies vaccine in the ED from January 2015 to June 2018 were included in the preimplementation control group and from December 2019 to November 2020 were included in the postimplementation intervention group. Data were analyzed in January 2021. The PEP bundle was implemented in December 2019 and consisted of electronic health record enhancements, including clinical decision support, ED staff education, and patient education. Full adherence to 6 human rabies immune globulin quality indicators: patient selection, dose, timing, infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock. The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women). Most patients presented to EDs embedded in a community hospital (231 patients [71%]). Full adherence increased from 37% in the preimplementation group to 61% postimplementation (absolute increase, 24%; 95% CI, 11% to 37%; P < .001). Adherence improved for quality indicators for infiltration into wounds (137 of 254 patients [54%] to 50 of 70 patients [71%]; P = .009), administration distant from rabies vaccine site (180 of 254 [71%] to 58 of 70 [83%]; P = .04), and administration that avoids the buttock (168 of 254 [66%] to 58 of 70 [83%]; P = .007). No instances of sciatic nerve injury or compartment syndrome were observed. In this quality improvement study, implementation of a rabies PEP bundle was associated with improved patient selection and delivery of human rabies immune globulin in EDs across a multihospital health system. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

Impact of the switch from four to three intradermal rabies post-exposure prophylaxis sessions in patients bitten by dogs: A cost-consequence analysis from the patients' perspective

The annual incidence of rabies deaths has been estimated in Cambodia at nearly 5.8/100,000 person-years. The cost of post exposure prophylaxis (PEP) and travel is potentially a significant barrier for exposed patients and their families, although safety nets are in place to provide the prophylaxis at no cost for low-income families. A decision-tree model was built to estimate changes in the costs from the patients' perspective and the survival outcomes of the Institut Pasteur du Cambodge (IPC) rabies PEP regimen after the switch from the Thai Red Cross (TRC) rabies PEP regimen in patients exposed to WHO category II or III bites by dogs. Derived from the IPC database, data included the trajectory of 203,497 patients, 1412 called-back patients and economic data on 201 patients. Uncertainty was addressed using one-way and probabilistic sensitivity analyses. Compared to the TRC regimen, the IPC regimen was cheaper and equally effective in patients with category II bites. In patients with category III bites, the IPC regimen was cheaper and its modeled probability of survival was 0.04% (95% CI, −0.12%; 0%) lower than the TRC regimen. However, the mortality rate was very low and the causes of death were uncertain. The data available may have lacked power to be able to statistically significantly tell apart the difference between genuine PEP failure and incorrect PEP administration, in the three versus the four-PEP sessions.

Factors Limiting the Appropriate Use of Rabies Post-exposure Prophylaxis by Health Professionals in Brazil.

Post-exposure prophylaxis (PEP) is necessary to prevent the fatal onset of rabies but requires optimization to avoid overuse in populations at risk of rabies. In Brazil, the incidence of dog bites remains high, with almost half of dog-bite patients not receiving the PEP recommended by the Ministry of Health guidelines between 2008 and 2017. In this study, we aimed to identify the factors that limit the appropriate prescribing of PEP by interviewing health professionals responsible for PEP administration and completion of the ‘Information System on Diseases of Compulsory Declaration’ (SINAN) form reporting human anti-rabies care for patients seeking health care after a dog bite. We conducted 147 questionnaires (45 questions each) in three Brazilian states (i.e., Rio Grande do Sul, Santa Catarina, Rio Grande do Norte) including questions related to the criteria used by professionals to classify a dog as “suspect” or “rabid”, knowledge on PEP prescription guidelines, SINAN and communication with veterinarians. Our analyses showed that most health professionals delivering PEP in these three states struggle to identify a rabies “suspect” dog according to the Ministry of Health guidelines, and to indicate the adequate PEP regimen, with only 11% of professionals prescribing the appropriate PEP under various dog-bite patient scenarios. PEP knowledge score was higher among professionals trained on PEP guidelines and working in facilities with the highest incidence of dog bites. In contrast, PEP knowledge scores did not vary significantly between states, and were not correlated to the professional's level of experience, the number of colleagues available at the health unit or the professional's confidence on prescribing appropriate PEP. Our results suggest that knowledge gaps in PEP administration among health professionals of Brazil can be reduced by implementing training programs to differentiate among rabies risk scenarios, prescribe the corresponding appropriate PEP and improve communication between health and veterinary authorities.

Response to a Serogroup B Meningococcal Disease Case Among Military Trainees

We describe the public health response to a military trainee who developed serogroup B meningococcal disease while sharing underwater breathing equipment. Despite high transmission risk, with rapid isolation and postexposure prophylaxis administration, there were no secondary cases. This case supports carefully weighing serogroup B meningococcal vaccination in high-risk settings.

Atypical paralytic rabies — A case-study from Kerala, India

Rabies, though endemic in India, has been a disease of low public health priority throughout the years. Being a non-notifiable disease together with limited diagnostic facilities, it often ends up in under-reporting of cases, especially atypical rabies. Failure of complete rabies Post Exposure Prophylaxis (PEP) with Immunoglobulin has been rarely reported. We report a case of atypical rabies in a 60-year-old man from a rural village in Kerala, who presented with fever, paralysis of limbs, fluctuating consciousness, phonophobia and without classical signs of hydrophobia and aerophobia 22 days after dog bite. The case is supplemented with supportive Magnetic Resonance Imaging (MRI) findings and corneal imprint smear Fluorescent Antibody Test (FAT). The death of the patient on the 28th day of exposure despite early PEP with rabies vaccine and immunoglobulin is suggestive of PEP failure. The case study stresses on the need in making rabies a notifiable disease in the study setting, encouraging disease specific investigation, ensuring availability of vaccine and immunoglobulins with adherence to standardized treatment protocols.Deviations from the recommended protocol for Animal bite management, such as delay in seeking PEP, lack of or improper administration of rabies immunoglobulin (e.g. missing out bite sites), lack of or improper primary wound care, and/or poor-quality rabies vaccine, may lead to death.

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

BackgroundAn 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 findingsTo 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.ConclusionsOur 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.

Validation of serum apolipoprotein A1 in rabies virus-infected mice as a biomarker for the preclinical diagnosis of rabies.

Rabies is a type of acute fetal encephalitis caused by rabies virus (RABV). While it becomes incurable after symptom onset, it can be prevented by post‐exposure prophylaxis (PEP) during the long incubation period. While preclinical diagnosis aids the appropriate PEP administration, it is mostly nonfeasible owing to the absence of viremia or a specific antibody response during the incubation period. Here, an attempt was made to identify a serum biomarker for the preclinical diagnosis of rabies. Using the serum from a mouse inoculated intramuscularly (i.m.) with 5 × 105 focus‐forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088/RFLuc) immediately before symptom onset, two‐dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up‐regulated. ELISA showed that the serum ApoA1 and specific antibody levels increased during the incubation period and on the day of symptom onset. Since a lower infectious dose can be used to induce the unstable and long incubation period generally observed in natural infection, the ApoA1 level in mice inoculated i.m. with 103 FFU of 1088/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up‐regulated in 50% and 58.3% of mice exhibiting robust RABV replication, respectively, but not in mice exhibiting weak RABV replication. In addition, it was reported that ApoA1 was found to be a biomarker for neuronal damage. Additional biomarker candidates will be needed for the effective preclinical diagnosis of rabies.

Assessing clinicians' Post-Exposure Prophylaxis recommendations for rabies virus exposures in Hunan Province, China.

BackgroundTimely and appropriate administration of post-exposure prophylaxis (PEP) is an essential component of human rabies prevention programs. We evaluated patient care at rabies clinics in a high-risk county in Hunan Province, China to inform strategies needed to achieve dog-mediated human rabies elimination by 2030.MethodsWe collected information on PEP, staff capacity, and service availability at the 17 rabies clinics in the high-risk county during onsite visits and key staff interviews. Additionally, we conducted observational assessments at five of these clinics, identified through purposive sampling to capture real-time information on patient care during a four-week period. Wound categories assigned by trained observers were considered accurate per national guidelines for comparison purposes. We used the kappa statistic and an alpha level of 0.05 to assess agreement between observers and clinic staff.ResultsIn 2015, the 17 clinics provided PEP to 5,261 patients. Although rabies vaccines were available at all 17 clinics, rabies immune globulin (RIG) was only available at the single urban clinic in the county. During the assessment period in 2016, 196 patients sought care for possible rabies virus exposures. According to observers, 88 (44%) patients had category III wounds, 104 (53%) had category II wounds and 4 (2%) had category I wounds. Observers and PEP clinic staff agreed on approximately half of the assigned wound categories (kappa = 0.55, p-value< 0.001). Agreement for the urban county-level CDC clinic (kappa = 0.93, p-value<0.001) was higher than for the township clinics (kappa = 0.16, p-value = 0.007). Using observer assigned wound categories, 142 (73%) patients received rabies vaccinations and RIG as outlined in the national guidelines.ConclusionRabies PEP services were available at each town of the project county; however, gaps between clinical practice and national rabies guidelines on the use of PEP were identified. We used these findings to develop and implement a training to rabies clinic staff on wound categorization, wound care, and appropriate use of PEP. Additional risk-based approaches for evaluating human rabies virus exposures may be needed as China progresses towards elimination.