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We conducted a clinical trial to assess the safety and putative efficacy of an additional human rabies immune globulin (HRIG; KEDRAB) versus an older product (Comparator, HyperRAB S/D® [Grifols]) and determine whether HRIG interferes with development of endogenous antibodies versus Comparator, when each is given with an active rabies vaccine. This was a prospective, double-blind, single-period, non-inferiority study in which subjects were randomized (1:1) to a single dose (20 IU/kg) of HRIG or Comparator on day 0 and rabies vaccine (RabAvert® [GlaxoSmithKline]; 1 mL of ≥2.5 IU/mL) on days 0, 3, 7, 14, and 28. Anti-rabies antibodies were measured by rapid fluorescent focus inhibition test on day 14, and subjects were followed until day 185. Rabies virus neutralizing antibody (RVNA) titers ≥0.5 IU/mL were considered seroconversion putatively indicative of protection. The non-inferiority criterion was the lower limit of the 90% confidence interval (CI) >-10%, for the between-group difference in the proportion of subjects achieving RVNA ≥0.5 IU/ mL. On day 14, 98.3% of 59 subjects in the HRIG group and 100% of 59 in the Comparator group had RVNA ≥0.5 IU/mL (difference between proportions -1.8%; 90% CI, -8.2, 3.1; non-inferiority criterion met). One subject in the HRIG group did not meet the seroconversion criteria for anti-rabies antibody, and one subject in the Comparator group showed an anamnestic response, with much higher than expected anti-rabies antibody levels at both baseline and on day 14. Thus, HRIG allows for prophylactic anti-rabies antibody titers and is non-inferior to Comparator, when administered with rabies vaccine.

Rabies is a deadly viral zoonosis with global disease burden. Following exposure to a rabid animal, postexposure prophylaxis (PEP) is the standard of care for unvaccinated persons. Despite the large proportion of pediatric cases, limited safety and efficacy data exist for use in pediatric patients. We report the safety, efficacy, and immunogenicity of a phase 4, prospective, 2-center, open-label, single-arm clinical trial evaluating human rabies immunoglobulin (HRIG150; KEDRAB 150 IU/mL) as part of PEP in patients (aged <17) with suspected or confirmed rabies exposure, where PEP was indicated. Thirty participants received 20 IU/kg HRIG150 infiltrated into the detectable wound site(s), with any remainder injected intramuscularly, concomitantly with the first of a 4-dose series (days 0, 3, 7, and 14) of rabies vaccine. Rabies virus neutralizing antibody (RVNA) titers and tolerability were assessed on day 14 following administration. Participant safety was monitored for 84 days. No serious adverse events, rabies infections, or deaths were recorded. Twenty-one participants (70.0%) experienced a total of 57 treatment-emergent adverse events (TEAEs) within 14 days following administration. Twelve participants (40.0%) experienced a total of 13 adverse events deemed treatment related. All TEAEs were mild in severity. On day 14, 28 participants (93.3%) had RVNA levels of ≥0.5 IU/mL (mean±standard deviation: 18.89 ± 31.61). These results demonstrate that HRIG150 is well tolerated and effective in pediatric patients as a component of PEP. To the authors' knowledge, this study is the first to establish pediatric safety and efficacy of HRIG in the US.

Rabies remains a global public health concern that is responsible for more than 59,000 human deaths per year [1]. Postexposure prophylaxis (PEP) for humans exposed to rabies virus should include wound cleansing followed by 1 dose of human rabies immunoglobulin (HRIG) and a series of cell culture rabies vaccine doses [2]. Symptomatic rabies is nearly always fatal but universally preventable with appropriate PEP. An estimated 30,000 to 60,000 Americans receive rabies PEP each year [3]. The stakeholders involved in PEP implementation in the United States are diverse, creating systematic complexity that creates barriers to accessing care, lacks coordination, and delivers suboptimal care. Here, we elaborate on 3 issues of (i) access to, (ii) coordination of, and (iii) delivery of care for suspected rabies exposures; share examples of contemporary quality initiatives from large health systems; and propose novel solutions.

ObjectivesTo compare the epidemiology of paediatric and adult patients receiving rabies immune globulin (RIG).DesignCross-sectional prevalence study.SettingEligible participants from the Symphony Integrated Dataverse presenting between 2013 and 2019.ParticipantsAll adult and paediatric patients with integrated claims and demographic data associated with RIG use from the Symphony Integrated Dataverse from 2013 to 2019.Primary and secondary outcome measuresPrevalence of diagnoses and procedures associated with paediatric and adult patient population based on frequency of International Classification of Diseases (ICD-9/ICD-10) and Current Procedural Terminology codes, respectively.MethodsWe used mutual information to identify features that differentiate the paediatric from adult patient population. Prevalence ratios were calculated to compare adult and paediatric patients.ResultsThere were 79 766 adult and 20 381 paediatric patients who met the inclusion criteria. Paediatric patients had a 5.92-fold higher prevalence of ‘open wounds to the head; neck; and trunk’, 3.10-fold higher prevalence of ‘abrasion or friction burn of face; neck; and scalp except eye; without mention of infection’, 4.44-fold higher prevalence of ‘open wound of scalp; without mention of complication’ and 6.75-fold higher prevalence of ‘laceration of skin of eyelid and periocular area | laceration of eyelid involving lacrimal passages’. Paediatric patients had a 3.83-fold higher prevalence of complex repairs compared with adult patients (n=157, 0.7% vs n=157, 0.2%, respectively).ConclusionsPaediatric patients represent a significant proportion of the patient population receiving RIG, and are associated with higher prevalence of codes reporting repair of larger, more complex wounds in highly innervated anatomical regions. Dosing and administration of RIG must be informed by animal bite wound characteristics; clinicians should understand the differences between presentations in adults and children and treat accordingly.