A 2016 article describes a pilot initiative exploring the efficacy of local infiltration of rabies immunoglobulins (RIG) as a cost-effective approach for passive immunization against rabies. The study involved 269 patients, who fell into the category III exposure group, bitten by suspected or confirmed rabid animals. Due to prohibitive cost with systemic weight-based dosing, this research focused on infiltrating the wounds locally with equine rabies immunoglobulin (ERIG) in amounts proportional to the wound size, irrespective of the patient's body weight, followed by a regular course of rabies vaccination using the intradermal route. Patients sought treatment within 72 hours of being bitten. The average dose was 1.26 mL of RIG that cost ~$3 with no deaths reported. This includes the subset of dog bite victims, which were all minimally followed for up to 9 months. A total of 30 serum samples were collected, which revealed all patients had antibody titers > 0.5 IU/mL by day 14. The earliest day of blood sampling was day 8. [1]
A 2000 brief article describes their nonrandomized assessment to explore the impact of injection sites on the efficacy of ERIG in patients with WHO category I or II rabies exposures. The cohort comprised 29 animal bite patients categorized by their Body Mass Index (BMI), including individuals characterized as normal, overweight, obese, and one underweight subject. The study employed a dose of 40 IU/kg of ERIG, following WHO-approved Thai Red Cross postexposure protocol with the administration of Purified Vero Cell Rabies Vaccine (PVRV). Group I received the ERIG injection in the gluteal region, targeting adipose tissue with a 23-gauge needle at a depth of 3.5 cm, while Group II had the ERIG injected into the deltoid muscle. Analysis of serum rabies neutralizing antibody levels conducted 24 and 72 hours post-injection revealed minimal detectable antibody titers across all participants, with no notable difference between injections into fat or muscle tissue. However, antibody levels remained below the WHO's acceptable threshold of 0.5 IU/mL, raising concerns about the early protective efficacy of the current dosing strategy. Only 2 patients achieved a titer level of 0.3 IU/mL at 24 hours, but dropped to 0.12 IU/mL 24 hours later. Therefore, patients requiring systemic treatment may not be sufficient with local infiltration alone. [2]
A 2017 animal study examined the role of systemic injection of RIG in conjunction with rabies vaccination. The research focused on assessing the levels of rabies virus-neutralizing antibodies in mice following administration of varying doses of RIG combined with rabies vaccine. BALB/c mice were divided into six groups receiving 0.80, 0.40, 0.20, 0.10, 0.05, or 0 IU of HRIG, injected intramuscularly in the gluteus on day 0, alongside a PVRV administered on the contralateral side. The findings from this investigation revealed no significant differences in antibody titers among the groups, indicating that systemic administration of RIG did not affect the efficacy of passive immunization or the production of neutralizing antibodies in adaptive immunization. The geometric mean titer values showed adequate levels of neutralizing antibodies against the rabies virus were only generated as a response to the rabies vaccine and not influenced by systemic RIG. These results emphasize the primary function of RIG being local infiltration at the wound site for rapid neutralization of the rabies virus, rather than contributing to systemic immunization, thus highlighting the critical importance of local wound infiltration in post-exposure prophylaxis for category III exposures. [3]
This preliminary study followed human rabies immune globulin (HRIG), labeled with technetium, by repeated scanning of the injection sites, kidneys and bladder in 8 adult rabbits. In the control studies, average radiotracer counts at the injection sites rapidly decreased from 63 to 18% at 0.5 h, and to 5% at 4 h. The isotope activity at the injection sites was not 100% on first scanning. We assume that this was due to the 5–7 min delay between injection and scanning. The radiotracer activity at the injection sites at 24 h was equal to background activity. In the HRIG study tagged with a radioactive isotope, retention of radioactive HRIG at the injected sites was impressive. An average of 57.9% activity was retained at 1 h and slowly decreased during the following 24 h to 24.4%. Activity at the injection sites was still clearly detectable at 24 h. There was more isotope activity over the liver compared with the control Tc-99m GHA group. This shows that HRIG is 75.6% systemically absorbed at around 24 h after injection at the site of administration. [4]