Defining the volume of rabies immunoglobulins/ rabies monoclonal antibodies requirement for wound infiltration of category III animal exposures - an exploratory study.

WHO recommends infiltration of rabies immunoglobulins/rabies monoclonal antibodies as anatomically possible, into or close to all category III animal bite wound(s)/exposures for post exposure prophylaxis. The volume required for wound infiltration depending upon the site/size/severity of wound is yet to be defined for guiding the treating physicians. This study aimed to determine the volume of rabies immunoglobulin/rabies monoclonal antibody required for wound infiltration depending upon the site, size, and severity. A prospective cohort study was conducted including category III animal exposures at the anti-rabies clinic, KIMS hospital and Research Center, Bangalore, India. The volume of rabies immunoglobulins/rabies monoclonal antibodies required for wound infiltration, depending on site, severity, and size was determined. All the subjects were followed for 6 months to demonstrate the safety and clinical efficacy of post exposure prophylaxis. The present study included 717 subjects having 1428 bite wounds. There was a significant difference in the median volume required for wound infiltration based on site, size, and severity of bite wounds. However, on pairwise comparison; the median volume among all the pairs for only wound size was found to be statistically significant. Supportively, a strong positive correlation was seen with the size of wound and volume infiltrated. The volume of rabies immunoglobulin/rabies monoclonal antibodies required for wound infiltration shall be determined according to size of wounds, i.e. 1 ml for <1 cm wound, 3 ml for 1-5 cm wound, and 5 ml for >5 cm wound.

Safety and Immunogenicity of purified chick embryo cell rabies vaccine (VaxiRab N) administered intradermally as post exposure prophylaxis.

The affordability to rabies vaccine for intramuscular administration in post exposure prophylaxis is a major constraint. Therefore, in countries, where there are financial constraints, World Health Organization recommends intradermal rabies vaccination that reduces the quantity and cost of vaccination. This study was done to evaluate the safety and immunogenicity of indigenously developed rabies vaccine (VaxiRab N) in comparison to a WHO recommended rabies vaccine (Rabipur) with demonstrated efficacy when administered by intradermal route using updated Thai Red Cross regimen. Eighty-six dog bite cases were randomly given either VaxiRab N (n = 43) or Rabipur (n = 43) as post exposure prophylaxis. The rabies virus neutralizing antibody concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluorescent focus inhibition test. The geometric mean RVNA concentration of both the groups were compared using t- test and was found that, P value > 0.05 on all days, thus showing no significant difference between the 2 groups. The adverse drug events were also compared using Z-test and was found to be not statistically significant (Z = 1.476, P = 0.139). In conclusion, VaxiRab N was found to be safe and effective in post exposure prophylaxis by intradermal route and was similar to the WHO recommended rabies vaccine (Rabipur) of demonstrated efficacy.

Assessing safety and immunogenicity of post-exposure prophylaxis following interchangeability of rabies vaccines in humans.

Rabies post exposure prophylaxis with cell culture vaccines by either intramuscular route or intradermal route spans over a period of one month. World Health Organization recommends completing post exposure prophylaxis against rabies with the same cell culture or embryonated egg rabies vaccine and with same route of administration and any deviation from this shall be an exception. In the present study, the safety and immunogenicity of rabies post-exposure prophylaxis was studied prospectively in 90 animal bite cases that had interchangeability of rabies vaccines either by route of administration or brand/type and such changes had occurred due to logistical/financial problems. Among them, 47 had change in route of administration from intramuscular to intradermal or vice versa and 43 had change in the brand/type of cell culture rabies vaccine. All of them had category III rabies exposure and received equine rabies immunoglobulin along with the rabies vaccine. None of the study subjects had any adverse reactions. The rabies virus neutralizing antibody titers was assessed by rapid fluorescent focus inhibition test and all the vaccinees had titers ≥0.5 IU per mL on day 14 which is considered as adequate for protection against rabies. Thus, the present study showed that, rabies post-exposure prophylaxis was safe and immunogenic despite changes in the route of administration and brand/type of rabies vaccine.

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines when administered by intradermal route: results of a metaanalysis.

The metadata of 10 published studies and 3 vaccine trial reports comprising of 19 vaccine cohorts from four countries conducted over a period of 23 years (1986 - 2009) was used for metaanalysis. The vaccines studied were purified chick embryo cell vaccine (Rabipur, India & Germany), purified vero cell rabies vaccine (Verorab, France; Indirab, India) & human diploid cell vaccine (MIRV, France).The potency of these vaccines varied from 0.55 IU to 2.32 IU per intradermal dose of 0.1 ml per site. The vaccines were administered to 1,011 subjects comprising of 19 cohorts and using five different ID regimens. The immunogenicity was measured by assays of rabies virus neutralizing antibody (RVNA) titres using rapid fluorescent focus inhibition test (RFFIT) [15 cohorts] and mouse neutralization test (MNT) [4 cohorts]. The statistical analysis of the data was done by Karl Pearson's correlation coefficient to measure the relationship between antigenicity and immunogenicity. It was revealed that, there was no significant linear relationship between antigenicity and immunogenicity of rabies vaccines when administered by intradermal route. (p> 0.230 and p>0.568).

Comparison of saftey and immunogenicity of purified chick embryo cell rabies vaccine (PCECV) and purified vero cell rabies vaccine (PVRV) using the Thai Red Cross intradermal regimen at a dose of 0.1 ML.

Intradermal (ID) vaccination with modern cell culture rabies vaccines is a means to significantly reduce the cost of post-exposure prophylaxis as compared to intramuscular vaccination. In this study we evaluated the efficacy, immunogenicity and tolerability of PCECV and PVRV administered ID in doses of 0.1 mL per site according to the 2-site Thai Red Cross (TRC) regimen. Patients with WHO category III exposure to suspect or laboratory proven rabid animals were administered either PCECV (n = 58) or PVRV (n = 52) ID at a dose of 0.1 mL per site at two sites on days 0, 3 and 7 and at one site on days 30 and 90. Serum samples were withdrawn on days 0, 14, 30, 90 and 180 and rabies virus neutralizing antibody (RVNA) titers were determined by rapid fluorescent focus inhibition test (RFFIT). Patients who were exposed to laboratory confirmed rabid animals were followed up for one year after exposure. All 110 patients developed RVNA titers above 0.5 IU/mL by day 14. Adequate titers >0.5 IU/mL were maintained up to day 180. Both vaccines induced equivalent RVNA titers at all time points and were well tolerated. Five subjects who were bitten by laboratory confirmed rabid dogs were alive and healthy one year after exposure. As demonstrated, PCECV and PVRV are both immunogenic, efficacious and well tolerated when administered in the TRC post-exposure prophylaxis regimen in ID doses of 0.1 mL as recommended by WHO guidelines. The use of PCECV in this regimen may prove more economical in developing countries like India.